Cheng H, Lederer M R, Xiao R P, Gómez A M, Zhou Y Y, Ziman B, Spurgeon H, Lakatta E G, Lederer W J
Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA.
Cell Calcium. 1996 Aug;20(2):129-40. doi: 10.1016/s0143-4160(96)90102-5.
Ca2+ sparks, the elementary units of sarcoplasmic reticulum (SR) Ca2+ release in cardiac, smooth and skeletal muscle are localized (2-4 microns ) increases in intracellular Ca2+ concentration, [Ca2+]i, that last briefly (30-100 ms). These Ca2+ sparks arise from the openings of a single SR Ca2+ release channel (ryanodine receptor, RyR) or a few RyRs acting in concert. In heart muscle, Ca2+ sparks can occur spontaneously in quiescent cells at a low rate (100 s-1 per cell). Identical Ca2+ sparks are also triggered by depolarization because the voltage-gated sarcolemmal L-type Ca2+ channels (dihydropyridine receptors, DHPRs) locally increase [Ca2+]i and thereby activate the RyRs by Ca(2+)-induced Ca2+ release (CICR). The exquisite responsiveness of this process, reflected by the ability of even a single DHPR to activate a Ca2+ spark, is perhaps due to the large local increase in [Ca2+]i in the vicinity of the RyR that is a consequence of the close apposition of the DHPRs and the RyRs. In this review we examine our current understanding of cardiac excitation-contraction (EC) coupling in light of recent studies on the elementary Ca2+ release events or Ca2+ sparks. In addition, we further characterized Ca2+ spark properties in rat and mouse heart cells. Specifically we have determined that: (i) Ca2+ sparks occur at the junctions between the transverse-tubules and the SR in both species; (ii) Ca2+ sparks are asymmetric, being 18% longer in the longitudinal direction than in the transverse direction; and (iii) Ca2+ sparks individually do not produce measurable sarcomere shortening (< 1%). These results are discussed with respect to local activation of the RyRs, the stability of CICR, Ca2+ diffusion, and the theory of EC coupling.
钙火花是心肌、平滑肌和骨骼肌中肌浆网（SR）钙释放的基本单位，是细胞内钙浓度[Ca2+]i局部（2 - 4微米）升高，持续时间短暂（30 - 100毫秒）。这些钙火花源于单个SR钙释放通道（雷诺丁受体，RyR）或少数协同作用的RyR的开放。在心肌中，静息细胞中钙火花可低频率自发出现（每个细胞100次/秒）。相同的钙火花也可由去极化触发，因为电压门控肌膜L型钙通道（二氢吡啶受体，DHPRs）使局部[Ca2+]i升高，从而通过钙诱导钙释放（CICR）激活RyR。即使单个DHPR就能激活一个钙火花，这一过程的敏锐反应性可能是由于DHPR与RyR紧密相邻，导致RyR附近[Ca2+]i大幅局部升高。在本综述中，我们根据对基本钙释放事件即钙火花的最新研究，审视我们目前对心脏兴奋 - 收缩（EC）偶联的理解。此外，我们进一步描述了大鼠和小鼠心脏细胞中钙火花的特性。具体而言，我们确定：（i）两种物种的钙火花均发生在横管与SR的连接处；（ii）钙火花不对称，纵向比横向长18%；（iii）单个钙火花不会产生可测量的肌节缩短（<1%）。我们结合RyR的局部激活、CICR的稳定性、钙扩散以及EC偶联理论对这些结果进行了讨论。
