Wier W G, López-López J R, Shacklock P S, Balke C W
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201, USA.
Ciba Found Symp. 1995;188:146-60; discussion 160-4. doi: 10.1002/9780470514696.ch9.
In heart cells, several distinct kinds of transient spatial patterns of cytoplasmic calcium ion concentration ([Ca2+]i) can be observed: (1) [Ca2+]i waves, in which regions of spontaneously increased [Ca2+]i propagate at high velocity (100 microns/s) through the cell; (2) Ca2+ 'sparks', which are spontaneous, non-propagating changes in [Ca2+]i that are localized in small (approximately 2 microns) subcellular regions; and (3) evoked [Ca2+]i transients that are elicited by electrical depolarization, in association with normal excitation-contraction (E-C) coupling. In confocal [Ca2+]i images, evoked [Ca2+]i transients appear to be nearly spatially uniform throughout the cell, except during their rising phase or during small depolarizations. In contrast to [Ca2+]i waves and spontaneous Ca2+ sparks, evoked [Ca2+]i transients are triggered by L-type Ca2+ channel current and they are 'controlled', in the sense that stopping the L-type Ca2+ current stops them. Despite their different characteristics, all three types of Ca2+ transient involve Ca(2+)-induced release of Ca2+ from the sarcoplasmic reticulum. Here, we address the question of how the autocatalytic process of Ca(2+)-induced Ca2+ release, which can easily be understood to underlie spontaneous regenerative ('uncontrolled'), propagating [Ca2+]i waves, might be 'harnessed', under other circumstances, to produce controlled changes in [Ca2+]i, as during normal excitation-contraction coupling, or changes in [Ca2+]i that do not propagate. We discuss our observations of Ca2+ waves, Ca2+ sparks and normal Ca2+ transients in heart cells and review our results on the 'gain' of Ca(2+)-induced Ca2+ release. We discuss a model involving Ca2+ microdomains beneath L-type Ca2+ channels, and clusters of Ca(2+)-activated Ca2+ release channels in the sarcoplasmic reticulum which may form the basis of the answer to this question.
在心脏细胞中，可以观察到几种不同类型的细胞质钙离子浓度（[Ca2+]i）的瞬时空间模式：（1）[Ca2+]i波，即自发[Ca2+]i增加的区域以高速（100微米/秒）在细胞中传播；（2）Ca2+“火花”，即[Ca2+]i的自发、非传播性变化，局限于小的（约2微米）亚细胞区域；（3）诱发的[Ca2+]i瞬变，由电去极化引发，与正常兴奋-收缩（E-C）偶联相关。在共聚焦[Ca2+]i图像中，诱发的[Ca2+]i瞬变在整个细胞中似乎在空间上几乎是均匀的，除了在其上升阶段或小去极化期间。与[Ca2+]i波和自发Ca2+火花不同，诱发的[Ca2+]i瞬变由L型Ca2+通道电流触发，并且在某种意义上是“可控的”，即停止L型Ca2+电流会使其停止。尽管它们具有不同的特征，但所有三种类型的Ca2+瞬变都涉及Ca2+诱导的Ca2+从肌浆网释放。在这里，我们探讨一个问题：Ca2+诱导的Ca2+释放的自催化过程，这一过程很容易被理解为自发再生（“不受控”）、传播的[Ca2+]i波的基础，在其他情况下，如何被“利用”来产生[Ca2+]i的可控变化，如在正常兴奋-收缩偶联期间，或产生不传播的[Ca2+]i变化。我们讨论了在心脏细胞中对Ca2+波、Ca2+火花和正常Ca2+瞬变的观察结果，并回顾了我们关于Ca2+诱导的Ca2+释放“增益”的结果。我们讨论了一个模型，该模型涉及L型Ca2+通道下方的Ca2+微区，以及肌浆网中Ca2+激活的Ca2+释放通道簇，这可能是这个问题答案的基础。
