Physiological modulation of inactivation in L-type Ca2+ channels:: one switch
Physiological modulation of inactivation in L-type Ca2+ channels:: one switch
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DOI：
10.1113/jphysiol.2003.047902
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发表时间：
2004-01-15
影响因子：
5.5
通讯作者：
Findlay, I
中科院分区：
文献类型：
--
作者：
Findlay, I
电压和Ca2+依赖的失活机制对l型Ca2+通道电流（I-CaL）衰减的相对贡献是一个古老的故事，最近的结果给了一个意想不到的转折。在心肌细胞中，电压依赖性失活（VDI）被认为是缓慢的，而由Ca2+内流和Ca2+诱导的Ca2+释放（CICR）引起的Ca2+依赖性失活（CDI）提供了一种自动负反馈机制，以限制Ca2+进入和I-CaL对心脏动作电位的贡献。β -肾上腺素能和毒蕈碱激动剂对I-CaL的生理调节基本上或多或少地通过增强或减少Ca2+通道活性、Ca2+内流、肌浆网负荷和CDI来参与。另一方面，最近的结果将VDI置于I-CaL监管的中心。在基本条件下，退极化增加了离子通道发生快速VDI的概率。这可以通过肾上腺素能刺激来预防。证据还表明，在CDI生效之前，显示快速VDI的通道失活。因此，VDI和CDI对I-CaL衰变的贡献是由快速VDI机制的开启、去极化和磷酸化关闭决定的。这些观点的生理学含义是，在基础条件下，I-CaL对动作电位的贡献将主要由电压和β -肾上腺素能刺激后的Ca2+决定。
The relative contributions of voltage- and Ca2+-dependent mechanisms of inactivation to the decay of L-type Ca2+ channel currents (I-CaL) is an old story to which recent results have given an unexpected twist. In cardiac myocytes voltage-dependent inactivation (VDI) was thought to be slow and Ca2+-dependent inactivation (CDI) resulting from Ca2+ influx and Ca2+-induced Ca2+-release (CICR) from the sarcoplasmic reticulum provided an automatic negative feedback mechanism to limit Ca2+ entry and the contribution of I-CaL to the cardiac action potential. Physiological modulation of I-CaL by beta-adrenergic and muscarinic agonists then involved essentially more or less of the same by enhancing or reducing Ca2+ channel activity, Ca2+ influx, sarcoplasmic reticulum load and thus CDI. Recent results on the other hand place VDI at the centre of the regulation of I-CaL. Under basal conditions it has been found that depolarization increases the probability that an ion channel will show rapid VDI. This is prevented by beta-adrenergic stimulation. Evidence also suggests that a channel which shows rapid VDI inactivates before CDI can become effective. Therefore the contributions of VDI and CDI to the decay of I-CaL are determined by the turning on, by depolarization, and the turning off, by phosphorylation, of the mechanism of rapid VDI. The physiological implications of these ideas are that under basal conditions the contribution of I-CaL to the action potential will be determined largely by voltage and by Ca2+ following beta-adrenergic stimulation.