Rhythmic ryanodine receptor Ca2+ releases during diastolic depolarization of sinoatrial pacemaker cells do not require membrane depolarization
Rhythmic ryanodine receptor Ca2+ releases during diastolic depolarization of sinoatrial pacemaker cells do not require membrane depolarization
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DOI：
10.1161/01.res.0000122045.55331.0f
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发表时间：
2004-04-02
影响因子：
20.1
通讯作者：
Lakatta, EG
中科院分区：
文献类型：
--
作者：
Vinogradova, TM;Zhou, YY;Lakatta, EG
窦房结细胞舒张期除极过程中，局部肌膜下钙释放（LCR）通过兰尼碱受体（RyRs）增加终末除极率。我们确定了兔窦房结细胞中的LCR是否需要同时发生膜去极化，或者本质上是节律性的，以及节律性是否与自发周期长度有关。共聚焦线扫描图像显示，在皂苷透性细胞和自发跳动的细胞急性电压钳位在最大舒张电位持续LCR。在电压钳制的初始阶段，LCR的时空特性与自发搏动的细胞或浸泡在150 nmol/L Ca~（2+）中的透化细胞没有区别。电压钳制期间持续节律性LCR的周期略短于电压钳制前的自发周期长度。在自发搏动的细胞中，在瞬态和稳态下，LCR周期与自发周期长度高度相关;无论周期长度如何，LCR主要发生在恒定的时间，即周期长度的80%至90%。数值模型模拟结合LCR再现实验结果。我们的结论是舒张期LCR反映了节律性的细胞内钙循环，不需要伴随的膜去极化，LCR周期性与自发周期长度密切相关。因此，窦房结起搏细胞的生物钟，就像自然界中发生的许多其他节律功能一样，涉及细胞内Ca 2+节律。
Localized, subsarcolemmal Ca2+ release (LCR) via ryanodine receptors (RyRs) during diastolic depolarization of sinoatrial nodal cells augments the terminal depolarization rate. We determined whether LCRs in rabbit sinoatrial nodal cells require the concurrent membrane depolarization, or are intrinsically rhythmic, and whether rhythmicity is linked to the spontaneous cycle length. Confocal linescan images revealed persistent LCRs both in saponin-permeabilized cells and in spontaneously beating cells acutely voltage-clamped at the maximum diastolic potential. During the initial stage of voltage clamp, the LCR spatiotemporal characteristics did not differ from those in spontaneously beating cells, or in permeabilized cells bathed in 150 nmol/L Ca2+. The period of persistent rhythmic LCRs during voltage clamp was slightly less than the spontaneous cycle length before voltage clamp. In spontaneously beating cells, in both transient and steady states, LCR period was highly correlated with the spontaneous cycle length; and regardless of the cycle length, LCRs occurred predominantly at a constant time, ie, 80% to 90% of the cycle length. Numerical model simulations incorporating LCRs reproduce the experimental results. We conclude that diastolic LCRs reflect rhythmic intracellular Ca2+ cycling that does not require the concomitant membrane depolarization, and that LCR periodicity is closely linked to the spontaneous cycle length. Thus, the biological clock of sinoatrial nodal pacemaker cells, like that of many other rhythmic functions occurring throughout nature, involves an intracellular Ca2+ rhythm.