Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences

The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on...
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Gespeichert in:

Autor*in:	Donald M Bers [verfasserIn] Stefano eMorotti [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	CaMKII calcium channel Calcium current inactivation Calcium current facilitation Calcium current staircase

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 5(2014)
Übergeordnetes Werk:	volume:5 ; year:2014

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2014.00144

Katalog-ID:	DOAJ078433606

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allfieldsGer	10.3389/fphar.2014.00144 doi (DE-627)DOAJ078433606 (DE-599)DOAJc6ffa789d1f543eda577e9a1cda5b81b DE-627 ger DE-627 rakwb eng RM1-950 Donald M Bers verfasserin aut Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on changes in ICa that occur during the cardiac action potential (AP), with particular attention to Ca2+-dependent inactivation (CDI), Ca2+-dependent facilitation (CDF) and how calmodulin (CaM) and Ca2+-CaM dependent protein kinase (CaMKII) participate in the regulation of Ca2+ current during the cardiac AP. CDI depends on CaM pre-bound to the C-terminal of the L-type Ca2+ channel, such that Ca2+ influx and Ca2+ released from the sarcoplasmic reticulum bind to that CaM and cause CDI. In cardiac myocytes CDI normally predominates over voltage-dependent inactivation. The decrease in ICa via CDI provides direct negative feedback on the overall Ca2+ influx during a single beat, when myocyte Ca2+ loading is high. CDF builds up over several beats, depends on CaMKII-dependent Ca2+ channel phosphorylation and results in a staircase of increasing ICa peak, with progressively slower inactivation. CDF and CDI co-exist and in combination may fine-tune the ICa waveform during the cardiac AP. CDF may partially compensate for the tendency for Ca2+ channel availability to decrease at higher heart rates because of accumulating inactivation. CDF may also allow some reactivation of ICa during long duration cardiac APs, and contribute to early afterdepolarizations, a form of triggered arrhythmias. CaMKII calcium channel Calcium current inactivation Calcium current facilitation Calcium current staircase Therapeutics. Pharmacology Stefano eMorotti verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 5(2014) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:5 year:2014 https://doi.org/10.3389/fphar.2014.00144 kostenfrei https://doaj.org/article/c6ffa789d1f543eda577e9a1cda5b81b kostenfrei http://journal.frontiersin.org/Journal/10.3389/fphar.2014.00144/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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 5 2014
allfieldsSound	10.3389/fphar.2014.00144 doi (DE-627)DOAJ078433606 (DE-599)DOAJc6ffa789d1f543eda577e9a1cda5b81b DE-627 ger DE-627 rakwb eng RM1-950 Donald M Bers verfasserin aut Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on changes in ICa that occur during the cardiac action potential (AP), with particular attention to Ca2+-dependent inactivation (CDI), Ca2+-dependent facilitation (CDF) and how calmodulin (CaM) and Ca2+-CaM dependent protein kinase (CaMKII) participate in the regulation of Ca2+ current during the cardiac AP. CDI depends on CaM pre-bound to the C-terminal of the L-type Ca2+ channel, such that Ca2+ influx and Ca2+ released from the sarcoplasmic reticulum bind to that CaM and cause CDI. In cardiac myocytes CDI normally predominates over voltage-dependent inactivation. The decrease in ICa via CDI provides direct negative feedback on the overall Ca2+ influx during a single beat, when myocyte Ca2+ loading is high. CDF builds up over several beats, depends on CaMKII-dependent Ca2+ channel phosphorylation and results in a staircase of increasing ICa peak, with progressively slower inactivation. CDF and CDI co-exist and in combination may fine-tune the ICa waveform during the cardiac AP. CDF may partially compensate for the tendency for Ca2+ channel availability to decrease at higher heart rates because of accumulating inactivation. CDF may also allow some reactivation of ICa during long duration cardiac APs, and contribute to early afterdepolarizations, a form of triggered arrhythmias. CaMKII calcium channel Calcium current inactivation Calcium current facilitation Calcium current staircase Therapeutics. Pharmacology Stefano eMorotti verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 5(2014) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:5 year:2014 https://doi.org/10.3389/fphar.2014.00144 kostenfrei https://doaj.org/article/c6ffa789d1f543eda577e9a1cda5b81b kostenfrei http://journal.frontiersin.org/Journal/10.3389/fphar.2014.00144/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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_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 5 2014
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topic_facet	CaMKII calcium channel Calcium current inactivation Calcium current facilitation Calcium current staircase Therapeutics. Pharmacology
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container_title	Frontiers in Pharmacology
authorswithroles_txt_mv	Donald M Bers @@aut@@ Stefano eMorotti @@aut@@
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callnumber-first	R - Medicine
author	Donald M Bers
spellingShingle	Donald M Bers misc RM1-950 misc CaMKII misc calcium channel misc Calcium current inactivation misc Calcium current facilitation misc Calcium current staircase misc Therapeutics. Pharmacology Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences
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topic_title	RM1-950 Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences CaMKII calcium channel Calcium current inactivation Calcium current facilitation Calcium current staircase
topic	misc RM1-950 misc CaMKII misc calcium channel misc Calcium current inactivation misc Calcium current facilitation misc Calcium current staircase misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc CaMKII misc calcium channel misc Calcium current inactivation misc Calcium current facilitation misc Calcium current staircase misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc CaMKII misc calcium channel misc Calcium current inactivation misc Calcium current facilitation misc Calcium current staircase misc Therapeutics. Pharmacology
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title	Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences
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title_full	Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences
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title_sort	ca2+ current facilitation is camkii-dependent and has arrhythmogenic consequences
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title_auth	Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences
abstract	The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on changes in ICa that occur during the cardiac action potential (AP), with particular attention to Ca2+-dependent inactivation (CDI), Ca2+-dependent facilitation (CDF) and how calmodulin (CaM) and Ca2+-CaM dependent protein kinase (CaMKII) participate in the regulation of Ca2+ current during the cardiac AP. CDI depends on CaM pre-bound to the C-terminal of the L-type Ca2+ channel, such that Ca2+ influx and Ca2+ released from the sarcoplasmic reticulum bind to that CaM and cause CDI. In cardiac myocytes CDI normally predominates over voltage-dependent inactivation. The decrease in ICa via CDI provides direct negative feedback on the overall Ca2+ influx during a single beat, when myocyte Ca2+ loading is high. CDF builds up over several beats, depends on CaMKII-dependent Ca2+ channel phosphorylation and results in a staircase of increasing ICa peak, with progressively slower inactivation. CDF and CDI co-exist and in combination may fine-tune the ICa waveform during the cardiac AP. CDF may partially compensate for the tendency for Ca2+ channel availability to decrease at higher heart rates because of accumulating inactivation. CDF may also allow some reactivation of ICa during long duration cardiac APs, and contribute to early afterdepolarizations, a form of triggered arrhythmias.
abstractGer	The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on changes in ICa that occur during the cardiac action potential (AP), with particular attention to Ca2+-dependent inactivation (CDI), Ca2+-dependent facilitation (CDF) and how calmodulin (CaM) and Ca2+-CaM dependent protein kinase (CaMKII) participate in the regulation of Ca2+ current during the cardiac AP. CDI depends on CaM pre-bound to the C-terminal of the L-type Ca2+ channel, such that Ca2+ influx and Ca2+ released from the sarcoplasmic reticulum bind to that CaM and cause CDI. In cardiac myocytes CDI normally predominates over voltage-dependent inactivation. The decrease in ICa via CDI provides direct negative feedback on the overall Ca2+ influx during a single beat, when myocyte Ca2+ loading is high. CDF builds up over several beats, depends on CaMKII-dependent Ca2+ channel phosphorylation and results in a staircase of increasing ICa peak, with progressively slower inactivation. CDF and CDI co-exist and in combination may fine-tune the ICa waveform during the cardiac AP. CDF may partially compensate for the tendency for Ca2+ channel availability to decrease at higher heart rates because of accumulating inactivation. CDF may also allow some reactivation of ICa during long duration cardiac APs, and contribute to early afterdepolarizations, a form of triggered arrhythmias.
abstract_unstemmed	The cardiac voltage gated Ca2+ current (ICa) is critical to the electrophysiological properties, excitation-contraction coupling, mitochondrial energetics and transcriptional regulation in heart. Thus, it is not surprising that cardiac ICa is regulated by numerous pathways. This review will focus on changes in ICa that occur during the cardiac action potential (AP), with particular attention to Ca2+-dependent inactivation (CDI), Ca2+-dependent facilitation (CDF) and how calmodulin (CaM) and Ca2+-CaM dependent protein kinase (CaMKII) participate in the regulation of Ca2+ current during the cardiac AP. CDI depends on CaM pre-bound to the C-terminal of the L-type Ca2+ channel, such that Ca2+ influx and Ca2+ released from the sarcoplasmic reticulum bind to that CaM and cause CDI. In cardiac myocytes CDI normally predominates over voltage-dependent inactivation. The decrease in ICa via CDI provides direct negative feedback on the overall Ca2+ influx during a single beat, when myocyte Ca2+ loading is high. CDF builds up over several beats, depends on CaMKII-dependent Ca2+ channel phosphorylation and results in a staircase of increasing ICa peak, with progressively slower inactivation. CDF and CDI co-exist and in combination may fine-tune the ICa waveform during the cardiac AP. CDF may partially compensate for the tendency for Ca2+ channel availability to decrease at higher heart rates because of accumulating inactivation. CDF may also allow some reactivation of ICa during long duration cardiac APs, and contribute to early afterdepolarizations, a form of triggered arrhythmias.
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title_short	Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences
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up_date	2024-07-03T17:56:51.359Z
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Ca2+ current facilitation is CaMKII-dependent and has arrhythmogenic consequences

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