Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies

Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward curre...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Jérôme Clatot [verfasserIn] Nathalie Neyroud [verfasserIn] Robert Cox [verfasserIn] Charlotte Souil [verfasserIn] Jing Huang [verfasserIn] Pascale Guicheney [verfasserIn] Charles Antzelevitch [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	arrhythmia Brugada syndrome spinocerebellar ataxia Na Kv4.3

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 21(2020), 14, p 5057
Übergeordnetes Werk:	volume:21 ; year:2020 ; number:14, p 5057

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms21145057

Katalog-ID:	DOAJ032875762

Internformat


LEADER	01000caa a22002652 4500
001	DOAJ032875762
003	DE-627
005	20240412223554.0
007	cr uuu---uuuuu
008	230226s2020 xx \|\|\|\|\|o 00\| \|\|eng c
024	7		\|a 10.3390/ijms21145057 \|2 doi
035			\|a (DE-627)DOAJ032875762
035			\|a (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14
040			\|a DE-627 \|b ger \|c DE-627 \|e rakwb
041			\|a eng
050		0	\|a QH301-705.5
050		0	\|a QD1-999
100	0		\|a Jérôme Clatot \|e verfasserin \|4 aut
245	1	0	\|a Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
264		1	\|c 2020
336			\|a Text \|b txt \|2 rdacontent
337			\|a Computermedien \|b c \|2 rdamedia
338			\|a Online-Ressource \|b cr \|2 rdacarrier
520			\|a Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.
650		4	\|a arrhythmia
650		4	\|a Brugada syndrome
650		4	\|a spinocerebellar ataxia
650		4	\|a Na<sub<v</sub<1.5
650		4	\|a <i<SCN5A</i<
650		4	\|a Kv4.3
653		0	\|a Biology (General)
653		0	\|a Chemistry
700	0		\|a Nathalie Neyroud \|e verfasserin \|4 aut
700	0		\|a Robert Cox \|e verfasserin \|4 aut
700	0		\|a Charlotte Souil \|e verfasserin \|4 aut
700	0		\|a Jing Huang \|e verfasserin \|4 aut
700	0		\|a Pascale Guicheney \|e verfasserin \|4 aut
700	0		\|a Charles Antzelevitch \|e verfasserin \|4 aut
773	0	8	\|i In \|t International Journal of Molecular Sciences \|d MDPI AG, 2003 \|g 21(2020), 14, p 5057 \|w (DE-627)316340715 \|w (DE-600)2019364-6 \|x 14220067 \|7 nnns
773	1	8	\|g volume:21 \|g year:2020 \|g number:14, p 5057
856	4	0	\|u https://doi.org/10.3390/ijms21145057 \|z kostenfrei
856	4	0	\|u https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 \|z kostenfrei
856	4	0	\|u https://www.mdpi.com/1422-0067/21/14/5057 \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1661-6596 \|y Journal toc \|z kostenfrei
856	4	2	\|u https://doaj.org/toc/1422-0067 \|y Journal toc \|z kostenfrei
912			\|a GBV_USEFLAG_A
912			\|a SYSFLAG_A
912			\|a GBV_DOAJ
912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
912			\|a GBV_ILN_23
912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
912			\|a GBV_ILN_39
912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_65
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_95
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 21 \|j 2020 \|e 14, p 5057

Indexfelder

author_variant	j c jc n n nn r c rc c s cs j h jh p g pg c a ca
matchkey_str	article:14220067:2020----::nergltookuvu4adotggtdoimhnesnelepeipstotcr
hierarchy_sort_str	2020
callnumber-subject-code	QH
publishDate	2020
allfields	10.3390/ijms21145057 doi (DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Jérôme Clatot verfasserin aut Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes. arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry Nathalie Neyroud verfasserin aut Robert Cox verfasserin aut Charlotte Souil verfasserin aut Jing Huang verfasserin aut Pascale Guicheney verfasserin aut Charles Antzelevitch verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 14, p 5057 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:14, p 5057 https://doi.org/10.3390/ijms21145057 kostenfrei https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 kostenfrei https://www.mdpi.com/1422-0067/21/14/5057 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 14, p 5057
spelling	10.3390/ijms21145057 doi (DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Jérôme Clatot verfasserin aut Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes. arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry Nathalie Neyroud verfasserin aut Robert Cox verfasserin aut Charlotte Souil verfasserin aut Jing Huang verfasserin aut Pascale Guicheney verfasserin aut Charles Antzelevitch verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 14, p 5057 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:14, p 5057 https://doi.org/10.3390/ijms21145057 kostenfrei https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 kostenfrei https://www.mdpi.com/1422-0067/21/14/5057 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 14, p 5057
allfields_unstemmed	10.3390/ijms21145057 doi (DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Jérôme Clatot verfasserin aut Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes. arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry Nathalie Neyroud verfasserin aut Robert Cox verfasserin aut Charlotte Souil verfasserin aut Jing Huang verfasserin aut Pascale Guicheney verfasserin aut Charles Antzelevitch verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 14, p 5057 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:14, p 5057 https://doi.org/10.3390/ijms21145057 kostenfrei https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 kostenfrei https://www.mdpi.com/1422-0067/21/14/5057 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 14, p 5057
allfieldsGer	10.3390/ijms21145057 doi (DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Jérôme Clatot verfasserin aut Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes. arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry Nathalie Neyroud verfasserin aut Robert Cox verfasserin aut Charlotte Souil verfasserin aut Jing Huang verfasserin aut Pascale Guicheney verfasserin aut Charles Antzelevitch verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 14, p 5057 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:14, p 5057 https://doi.org/10.3390/ijms21145057 kostenfrei https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 kostenfrei https://www.mdpi.com/1422-0067/21/14/5057 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 14, p 5057
allfieldsSound	10.3390/ijms21145057 doi (DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Jérôme Clatot verfasserin aut Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes. arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry Nathalie Neyroud verfasserin aut Robert Cox verfasserin aut Charlotte Souil verfasserin aut Jing Huang verfasserin aut Pascale Guicheney verfasserin aut Charles Antzelevitch verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 14, p 5057 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:14, p 5057 https://doi.org/10.3390/ijms21145057 kostenfrei https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 kostenfrei https://www.mdpi.com/1422-0067/21/14/5057 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 14, p 5057
language	English
source	In International Journal of Molecular Sciences 21(2020), 14, p 5057 volume:21 year:2020 number:14, p 5057
sourceStr	In International Journal of Molecular Sciences 21(2020), 14, p 5057 volume:21 year:2020 number:14, p 5057
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3 Biology (General) Chemistry
isfreeaccess_bool	true
container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Jérôme Clatot @@aut@@ Nathalie Neyroud @@aut@@ Robert Cox @@aut@@ Charlotte Souil @@aut@@ Jing Huang @@aut@@ Pascale Guicheney @@aut@@ Charles Antzelevitch @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ032875762
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ032875762</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240412223554.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230226s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/ijms21145057</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ032875762</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH301-705.5</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QD1-999</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jérôme Clatot</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">arrhythmia</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brugada syndrome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">spinocerebellar ataxia</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Na<sub<v</sub<1.5</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a"><i<SCN5A</i<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kv4.3</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Chemistry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nathalie Neyroud</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert Cox</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charlotte Souil</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jing Huang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pascale Guicheney</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charles Antzelevitch</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">International Journal of Molecular Sciences</subfield><subfield code="d">MDPI AG, 2003</subfield><subfield code="g">21(2020), 14, p 5057</subfield><subfield code="w">(DE-627)316340715</subfield><subfield code="w">(DE-600)2019364-6</subfield><subfield code="x">14220067</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:21</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:14, p 5057</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/ijms21145057</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/1422-0067/21/14/5057</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1661-6596</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1422-0067</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">21</subfield><subfield code="j">2020</subfield><subfield code="e">14, p 5057</subfield></datafield></record></collection>
callnumber-first	Q - Science
author	Jérôme Clatot
spellingShingle	Jérôme Clatot misc QH301-705.5 misc QD1-999 misc arrhythmia misc Brugada syndrome misc spinocerebellar ataxia misc Na<sub<v</sub<1.5 misc <i<SCN5A</i< misc Kv4.3 misc Biology (General) misc Chemistry Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
authorStr	Jérôme Clatot
ppnlink_with_tag_str_mv	@@773@@(DE-627)316340715
format	electronic Article
delete_txt_mv	keep
author_role	aut aut aut aut aut aut aut
collection	DOAJ
remote_str	true
callnumber-label	QH301-705
illustrated	Not Illustrated
issn	14220067
topic_title	QH301-705.5 QD1-999 Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies arrhythmia Brugada syndrome spinocerebellar ataxia Na<sub<v</sub<1.5 <i<SCN5A</i< Kv4.3
topic	misc QH301-705.5 misc QD1-999 misc arrhythmia misc Brugada syndrome misc spinocerebellar ataxia misc Na<sub<v</sub<1.5 misc <i<SCN5A</i< misc Kv4.3 misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc arrhythmia misc Brugada syndrome misc spinocerebellar ataxia misc Na<sub<v</sub<1.5 misc <i<SCN5A</i< misc Kv4.3 misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc arrhythmia misc Brugada syndrome misc spinocerebellar ataxia misc Na<sub<v</sub<1.5 misc <i<SCN5A</i< misc Kv4.3 misc Biology (General) misc Chemistry
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
format_main_str_mv	Text Zeitschrift/Artikel
carriertype_str_mv	cr
hierarchy_parent_title	International Journal of Molecular Sciences
hierarchy_parent_id	316340715
hierarchy_top_title	International Journal of Molecular Sciences
isfreeaccess_txt	true
familylinks_str_mv	(DE-627)316340715 (DE-600)2019364-6
title	Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
ctrlnum	(DE-627)DOAJ032875762 (DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14
title_full	Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
author_sort	Jérôme Clatot
journal	International Journal of Molecular Sciences
journalStr	International Journal of Molecular Sciences
callnumber-first-code	Q
lang_code	eng
isOA_bool	true
recordtype	marc
publishDateSort	2020
contenttype_str_mv	txt
author_browse	Jérôme Clatot Nathalie Neyroud Robert Cox Charlotte Souil Jing Huang Pascale Guicheney Charles Antzelevitch
container_volume	21
class	QH301-705.5 QD1-999
format_se	Elektronische Aufsätze
author-letter	Jérôme Clatot
doi_str_mv	10.3390/ijms21145057
author2-role	verfasserin
title_sort	inter-regulation of k<sub<v</sub<4.3 and voltage-gated sodium channels underlies predisposition to cardiac and neuronal channelopathies
callnumber	QH301-705.5
title_auth	Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
abstract	Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.
abstractGer	Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.
abstract_unstemmed	Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
container_issue	14, p 5057
title_short	Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies
url	https://doi.org/10.3390/ijms21145057 https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14 https://www.mdpi.com/1422-0067/21/14/5057 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
remote_bool	true
author2	Nathalie Neyroud Robert Cox Charlotte Souil Jing Huang Pascale Guicheney Charles Antzelevitch
author2Str	Nathalie Neyroud Robert Cox Charlotte Souil Jing Huang Pascale Guicheney Charles Antzelevitch
ppnlink	316340715
callnumber-subject	QH - Natural History and Biology
mediatype_str_mv	c
isOA_txt	true
hochschulschrift_bool	false
doi_str	10.3390/ijms21145057
callnumber-a	QH301-705.5
up_date	2024-07-03T14:35:14.785Z
_version_	1803568875866947584
fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ032875762</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240412223554.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230226s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.3390/ijms21145057</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ032875762</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJe0a1fbddbad74b9199aa0c3f1f71bd14</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QH301-705.5</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">QD1-999</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Jérôme Clatot</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background: Genetic variants in voltage-gated sodium channels (Na<sub<v</sub<) encoded by <i<SCNXA</i< genes, responsible for I<sub<Na</sub<, and K<sub<v</sub<4.3 channels encoded by <i<KCND3</i<, responsible for the transient outward current (I<sub<to</sub<), contribute to the manifestation of both Brugada syndrome (BrS) and spinocerebellar ataxia (SCA19/22). We examined the hypothesis that K<sub<v</sub<4.3 and Na<sub<v</sub< variants regulate each other’s function, thus modulating I<sub<Na</sub</I<sub<to</sub< balance in cardiomyocytes and I<sub<Na</sub</I<sub<(A)</sub< balance in neurons. Methods: Bicistronic and other constructs were used to express WT or variant Na<sub<v</sub<1.5 and K<sub<v</sub<4.3 channels in HEK293 cells. I<sub<Na</sub< and I<sub<to</sub< were recorded. Results: <i<SCN5A</i< variants associated with BrS reduced I<sub<Na</sub<, but increased I<sub<to</sub<. Moreover, BrS and SCA19/22 <i<KCND3</i< variants associated with a gain of function of I<sub<to</sub<, significantly reduced I<sub<Na</sub<, whereas the SCA19/22 <i<KCND3</i< variants associated with a loss of function (LOF) of I<sub<to</sub< significantly increased I<sub<Na</sub<. Auxiliary subunits Na<sub<v</sub<β1, MiRP3 and KChIP2 also modulated I<sub<Na</sub</I<sub<to</sub< balance. Co-immunoprecipitation and Duolink studies suggested that the two channels interact within the intracellular compartments and biotinylation showed that LOF <i<SCN5A</i< variants can increase K<sub<v</sub<4.3 cell-surface expression. Conclusion: Na<sub<v</sub< and K<sub<v</sub<4.3 channels modulate each other’s function via trafficking and gating mechanisms, which have important implications for improved understanding of these allelic cardiac and neuronal syndromes.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">arrhythmia</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Brugada syndrome</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">spinocerebellar ataxia</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Na<sub<v</sub<1.5</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a"><i<SCN5A</i<</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kv4.3</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Biology (General)</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Chemistry</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Nathalie Neyroud</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Robert Cox</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charlotte Souil</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jing Huang</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Pascale Guicheney</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Charles Antzelevitch</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">International Journal of Molecular Sciences</subfield><subfield code="d">MDPI AG, 2003</subfield><subfield code="g">21(2020), 14, p 5057</subfield><subfield code="w">(DE-627)316340715</subfield><subfield code="w">(DE-600)2019364-6</subfield><subfield code="x">14220067</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:21</subfield><subfield code="g">year:2020</subfield><subfield code="g">number:14, p 5057</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.3390/ijms21145057</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/e0a1fbddbad74b9199aa0c3f1f71bd14</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://www.mdpi.com/1422-0067/21/14/5057</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1661-6596</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/1422-0067</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_31</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_70</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_224</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2005</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2009</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2011</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2055</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2111</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">21</subfield><subfield code="j">2020</subfield><subfield code="e">14, p 5057</subfield></datafield></record></collection>
score	7.402916

Nicht das Richtige dabei?

Schreiben Sie uns!

Inter-Regulation of K<sub<v</sub<4.3 and Voltage-Gated Sodium Channels Underlies Predisposition to Cardiac and Neuronal Channelopathies

Nicht das Richtige dabei?

Zugang & Verfügbarkeit

Vorhandene Bände

Nicht das Richtige dabei?