The effects of membrane potential, SR Ca2+ content and RyR responsiveness on systolic Ca2+ alternans in rat ventricular myocytes
The effects of membrane potential, SR Ca2+ content and RyR responsiveness on systolic Ca2+ alternans in rat ventricular myocytes
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DOI：
10.1113/jphysiol.2008.164368
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发表时间：
2009-03-15
影响因子：
5.5
通讯作者：
O'Neill, Stephen
中科院分区：
文献类型：
--
作者：
Li, Yatong;Diaz, Mary E.;O'Neill, Stephen
先前的工作表明，小的去极化脉冲在心室肌细胞的收缩期钙瞬变的幅度中产生节拍交替。本工作的目的是探讨肌浆网钙离子含量和L钙电流的变化在该交替放电中的作用。当去极化脉冲的幅度从10 mV增加到30 mV时，交替波的幅度减小。激光共聚焦扫描研究表明，伴随这一现象的是钙波传播部位的数量增加。去极化幅度的突然降低导致了三种行为：(1)交替发生前，钙瞬变幅度逐渐降低，伴随着SR钙的丢失；(2)交替发生前，钙瞬变幅度逐渐增加，伴随着SR钙的增加；(3)交替发生时，SR含量没有变化。我们得出结论，只要SR中有足够的Ca~(2+)维持波的传播，如果SR中有足够的Ca~(2+)维持波的传播，那么如果SR中L类通道开放的减少和SR Ca~(2+)含量的变化共同导致SR的空间碎片释放，就会发生交替。低浓度咖啡因(100微米)可增强兰尼定受体(RyR)的开放，使交替波消失几个脉冲，但一旦肌质网钙离子含量降至新的电波传播阈值，交替波就会重新形成。最后，我们证明了用200微米的Cd~(2+)抑制L型钙电流可通过类似的钙离子释放谱的碎裂和钙离子释放小波的传播而产生交替。
Previous work has shown that small depolarizing pulses produce a beat to beat alternation in the amplitude of the systolic Ca2+ transient in ventricular myocytes. The aim of the present work was to investigate the role of changes of SR Ca2+ content and L-type Ca2+ current in this alternans. As the amplitude of the depolarizing pulse was increased from 10 to 30 mV the magnitude of alternans decreased. Confocal linescan studies showed that this was accompanied by an increase in the number of sites from which Ca2+ waves propagated. A sudden decrease in the depolarisation amplitude resulted in three classes of behaviour: (1) a gradual decrease in Ca2+ transient amplitude before alternans developed accompanied by a loss of SR Ca2+, (2) a gradual increase in Ca2+ transient amplitude before alternans accompanied by a gain of SR Ca2+, and (3) immediate development of alternans with no change of SR content. We conclude that alternans develops if the combination of decreased opening of L-type channels and change of SR Ca2+ content results in spatially fragmented release from the SR as long as there is sufficient Ca2+ in the SR to sustain wave propagation. Potentiation of the opening of the ryanodine receptor (RyR) by low concentrations of caffeine (100 mu m) abolished alternans for a few pulses but the alternans then redeveloped once SR Ca2+ content fell to the new threshold for wave propagation. Finally we show evidence that inhibiting L-type Ca2+ current with 200 mu m Cd2+ produces alternans by means of a similar fragmentation of the Ca2+ release profile and propagation of mini-waves of Ca2+ release.