Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis

Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evid...
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Autor*in:	Ioannis Markakis [verfasserIn] Ioannis Charitakis [verfasserIn] Christine Beeton [verfasserIn] Melpomeni Galani [verfasserIn] Elpida Repousi [verfasserIn] Stella Aggeloglou [verfasserIn] Petros P. Sfikakis [verfasserIn] Michael W. Pennington [verfasserIn] K. George Chandy [verfasserIn] Cornelia Poulopoulou [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 12(2021)
Übergeordnetes Werk:	volume:12 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2021.714841

Katalog-ID:	DOAJ003172228

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spelling	10.3389/fphar.2021.714841 doi (DE-627)DOAJ003172228 (DE-599)DOAJ0f9684dd16cb45ed9e75cfffbfd1bd3a DE-627 ger DE-627 rakwb eng RM1-950 Ioannis Markakis verfasserin aut Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease. T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation Therapeutics. Pharmacology Ioannis Markakis verfasserin aut Ioannis Charitakis verfasserin aut Christine Beeton verfasserin aut Christine Beeton verfasserin aut Melpomeni Galani verfasserin aut Elpida Repousi verfasserin aut Elpida Repousi verfasserin aut Stella Aggeloglou verfasserin aut Petros P. Sfikakis verfasserin aut Michael W. Pennington verfasserin aut K. George Chandy verfasserin aut K. George Chandy verfasserin aut Cornelia Poulopoulou verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 12(2021) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:12 year:2021 https://doi.org/10.3389/fphar.2021.714841 kostenfrei https://doaj.org/article/0f9684dd16cb45ed9e75cfffbfd1bd3a kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 12 2021
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allfieldsSound	10.3389/fphar.2021.714841 doi (DE-627)DOAJ003172228 (DE-599)DOAJ0f9684dd16cb45ed9e75cfffbfd1bd3a DE-627 ger DE-627 rakwb eng RM1-950 Ioannis Markakis verfasserin aut Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease. T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation Therapeutics. Pharmacology Ioannis Markakis verfasserin aut Ioannis Charitakis verfasserin aut Christine Beeton verfasserin aut Christine Beeton verfasserin aut Melpomeni Galani verfasserin aut Elpida Repousi verfasserin aut Elpida Repousi verfasserin aut Stella Aggeloglou verfasserin aut Petros P. Sfikakis verfasserin aut Michael W. Pennington verfasserin aut K. George Chandy verfasserin aut K. George Chandy verfasserin aut Cornelia Poulopoulou verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 12(2021) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:12 year:2021 https://doi.org/10.3389/fphar.2021.714841 kostenfrei https://doaj.org/article/0f9684dd16cb45ed9e75cfffbfd1bd3a kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 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_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_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 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 12 2021
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callnumber-first	R - Medicine
author	Ioannis Markakis
spellingShingle	Ioannis Markakis misc RM1-950 misc T cells misc potassium channels misc Kv1.3 misc multiple sclerosis misc patch clamp misc calcium regulation misc Therapeutics. Pharmacology Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
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topic_title	RM1-950 Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis T cells potassium channels Kv1.3 multiple sclerosis patch clamp calcium regulation
topic	misc RM1-950 misc T cells misc potassium channels misc Kv1.3 misc multiple sclerosis misc patch clamp misc calcium regulation misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc T cells misc potassium channels misc Kv1.3 misc multiple sclerosis misc patch clamp misc calcium regulation misc Therapeutics. Pharmacology
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title	Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
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title_full	Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
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author_browse	Ioannis Markakis Ioannis Charitakis Christine Beeton Melpomeni Galani Elpida Repousi Stella Aggeloglou Petros P. Sfikakis Michael W. Pennington K. George Chandy Cornelia Poulopoulou
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title_sort	kv1.3 channel up-regulation in peripheral blood t lymphocytes of patients with multiple sclerosis
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title_auth	Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
abstract	Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.
abstractGer	Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.
abstract_unstemmed	Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p < 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p < 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.
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title_short	Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis
url	https://doi.org/10.3389/fphar.2021.714841 https://doaj.org/article/0f9684dd16cb45ed9e75cfffbfd1bd3a https://www.frontiersin.org/articles/10.3389/fphar.2021.714841/full https://doaj.org/toc/1663-9812
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It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy and disease controls. Our data demonstrate that T lymphocytes in MS, manifest a significant up-regulation of Kv1.3 mRNA, Kv1.3 membrane protein and Kv1.3 current density and therefore of functional membrane channel protein, compared to control groups (p &lt; 0.001). Interestingly, patient sub-grouping shows that Kv1.3 channel density is significantly higher in secondary progressive, compared to relapsing-remitting multiple sclerosis (p &lt; 0.001). Taking into account the tight connection between Kv1.3 channel activity and calcium-dependent processes, our data predict and could partly explain the reported alterations of T lymphocyte function in multiple sclerosis, while they highlight Kv1.3 channels as potential therapeutic targets and peripheral biomarkers for the disease.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">T cells</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">potassium channels</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Kv1.3</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">multiple sclerosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">patch clamp</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">calcium regulation</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Therapeutics. 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Kv1.3 Channel Up-Regulation in Peripheral Blood T Lymphocytes of Patients With Multiple Sclerosis

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