Ca(2+) current facilitation is CaMKII-dependent and has arrhythmogenic consequences.
Ca(2+) current facilitation is CaMKII-dependent and has arrhythmogenic consequences.
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DOI：
10.3389/fphar.2014.00144
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发表时间：
2014
影响因子：
5.6
通讯作者：
Morotti S
中科院分区：
文献类型：
--
作者：
Bers DM;Morotti S
心脏电压门控Ca2+电流（ICa）对心脏电生理特性、兴奋-收缩耦合、线粒体能量学和转录调节至关重要。因此，心脏ICa受多种途径调控并不奇怪。这篇综述将集中在心脏动作电位（AP）期间发生的ICa变化，特别关注Ca2+依赖性失活（CDI）， Ca2+依赖性促进（CDF）以及钙调蛋白（CaM）和Ca2+-CaM依赖性蛋白激酶（CaMKII）如何参与心脏AP期间Ca2+电流的调节。CDI依赖于CaM预结合到l型Ca2+通道的c端。Ca2+内流和肌浆网释放的Ca2+与CaM结合并引起CDI。在心肌细胞中，CDI通常优于电压依赖性失活。当心肌细胞Ca2+负荷高时，通过CDI减少的ICa对单次搏动期间的总体Ca2+内流提供了直接的负反馈。CDF在几次心跳中积累，依赖于camkii依赖的Ca2+通道磷酸化，并导致ICa峰逐渐增加，失活速度逐渐减慢。CDF和CDI共存，并结合可能微调心脏AP期间的ICa波形。CDF可能部分补偿Ca2+通道可用性在高心率下由于累积失活而降低的趋势。CDF也可能在长时间心脏ap期间允许ICa重新激活，并有助于早期后去极化，这是一种触发性心律失常的形式。
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 pre-dominates 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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影响因子：
37.8
作者：
Despa, S;Islam, MA;Bers, DM
通讯作者：
Bers, DM
DOI：
10.1073/pnas.262372999
发表时间：
2002-12-24
影响因子：
11.1
作者：
Alseikhan, BA;DeMaria, CD;Yue, DT
通讯作者：
Yue, DT
影响因子：
56.9
作者：
De Koninck, P;Schulman, H
通讯作者：
Schulman, H
DOI：
10.1152/ajpheart.00469.2006
发表时间：
2007-07-01
影响因子：
4.8
作者：
Altamirano, Julio;Bers, Donald M.
通讯作者：
Bers, Donald M.
DOI：
10.1073/pnas.0914287107
发表时间：
2010-06-01
影响因子：
11.1
作者：
Blaich, Anne;Welling, Andrea;Moosmang, Sven
通讯作者：
Moosmang, Sven