Gain and cardiac E-C coupling: revisited and revised.
Gain and cardiac E-C coupling: revisited and revised.
复制标题
增益和心脏 E-C 耦合：重新审视和修订。
DOI：
10.1161/circresaha.107.160929
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发表时间：
2007
影响因子：
20.1
通讯作者：
Wier,WithrowGil
中科院分区：
文献类型：
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作者：
Wier,WithrowGil
心脏内皮细胞偶联中的“增益”现象引起了大量的实验研究和理论推测。所谓“宏观”或“全细胞”增益可定义为通过SR钙释放通道(RyR)的总流量与通过L型钙通道(LCC)的总流量之比。在实验上，早期发现Gain相对较高，这一观察结果，加上似乎不相容的事实，即钙诱导的钙释放(CICR)通常在心肌中受到严格控制，导致了对心脏EC偶联的现代理解，即“局部控制”理论的发展。Gain不仅反映了构成正常EC偶联的基本过程的运行，而且还反映了心脏的重要病理状况，特别是那些由不受控制的SR钙释放所产生的过程，如触发的心律失常。1在心脏，可以说“并不是所有的钙电流(ICa)都是平等的”；负电位的ICa比正电位的等量(峰值)ICa更能有效地触发SR的钙释放。因此，激活电压越正，增益就越小。对这一现象的传统和广泛接受的解释是基于单通道(单位)钙电流(ICa)的电压依赖性，并由Stern和他的同事简洁地指出，2“增益随着电压的降低而减少，因为L型电流触发RyR释放的有效性取决于L型通道的单一电流，随着钙反转电位的接近，增益减小”。事实上，这是心脏内皮细胞偶联的局部控制理论的基石。然而，早期人们(也被Stern)认识到，“这两条曲线(钙电流和肌浆钙释放)之间的差异实际上是一个线索，一方面激活的肌膜通道的数量和它们的单一电流的大小在控制钙释放方面扮演着根本不同的角色……”在15年后的这一期《循环研究》中，阿尔塔米拉诺和贝尔斯报告了在实验上首次确定这两个因素的不同作用的真正进展，这两个因素是激活的L型钙通道的数量(N*Po)和钙通道的大小
A phenomenon that has fostered much experimental investigation and theoretical speculation is “gain” in cardiac EC coupling. So-called “macroscopic” or “wholecell” gain may be defined as the ratio of the total flux through the SR Ca2 release channels (RyR) to that through the L-type Ca2 channels (LCC). Experimentally, gain was found early on to be relatively high, and this observation, together with the seemingly incompatible fact that Ca2-induced Ca2 release (CICR) is normally tightly controlled in cardiac muscle, led to the development of the modern understanding of cardiac EC coupling, the “local control” theory. Gain reflects not only the operation of the fundamental processes that underlie normal EC coupling, but also those involved in important pathological conditions of the heart, particularly those produced by uncontrolled SR Ca2 release, such as triggered arrhythmias. 1In the heart, it can be said that “not all Ca2 currents (ICa) are created equal”; ICa at negative potentials is much more efficacious in triggering SR Ca2 release than is equivalent (peak) ICa at positive potentials. Therefore, gain decreases as activating voltage is made more positive. The conventional and widely accepted explanation of this phenomenon is based on the voltage-dependence of the single-channel (unitary) Ca2 current (iCa), and was stated succinctly by Stern and his colleagues, 2 “gain decreases with voltage because the efficacy of the L-type current to trigger release from the RyR depends on the unitary current of the L-type channel, which decreases as the calcium reversal potential is approached”. Indeed this is a cornerstone of the local control theory of cardiac EC coupling. However, early on it had been recognized3 (also by Stern) that “the discrepancy between these two curves (Ca2 current and SR Ca2 release) is actually a clue to the fact that the number of sarcolemmal channels activated, on the one hand, and the magnitude of their unitary current, on the other, play fundamentally different roles in controlling calcium release...”. In this issue of Circulation Research, 15 years later, Altamirano and Bers4 report real progress in defining experimentally for the first time the different roles of these 2 factors, the number of L-type Ca2channels activated (N* Po), and the magnitude of the Ca2