Phase-dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload.
Phase-dependent properties of the cardiac sarcoplasmic reticulum oscillator in cat right atrium: a mechanism contributing to dysrhythmias induced by Ca2+ overload.
复制标题
猫右心房心脏肌浆网振荡器的相位依赖性特性：Ca2超载引起心律失常的机制。
DOI：
10.1113/expphysiol.1993.sp003672
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发表时间：
1993
影响因子：
2.7
通讯作者：
Lipsius,SL
中科院分区：
文献类型：
--
作者：
Rubenstein,DS;Zbilut,JP;WebberJr,CL;Lipsius,SL
这些实验分析了 Ca2+ 超载引起的肌浆网 (SR) 自发振荡的相位依赖性特性。通过将右心房组织暴露于含有 50% 正常 Na+ 和 0.5 mM K+ 的改良 Tyrode 溶液中，使细胞内 Ca2+ 负载。添加维拉帕米 (2 microM) 以阻止再生活动。细胞内 Ca2+ 过载引起自发的、有节律的电压和张力振荡，这些振荡是 1:1 锁相的。通过暴露于低 (0.9 mM) 外部 Ca2+、1 µM 兰尼碱或 10 mM 咖啡因，电压和张力振荡被消除，表明电压和张力振荡都是由 SR Ca2+ 释放中的自发振荡引起的。神经刺激的乙酰胆碱释放的单脉冲引起电压和张力振荡的相移。正弦电流用作周期性刺激来驱动膜电压并引起周期性电压振荡。受激电压振荡在接近基本自发 SR 振荡周期长度的频率范围内以 1:1 的比例夹带自发张力振荡，或者在接近自发 SR 振荡周期长度一半的频率范围内以 2:1 的比例夹带自发张力振荡。这两个区域之间的刺激频率以可预测的固定耦合比（4:3、3:2）夹带张力振荡，并产生类似温克贝克的电压模式。锁相区域之间的刺激频率导致复杂的耦合关系和不规则的电压模式。暴露于 1 µM 兰尼碱、0.9 mM 外部 Ca2+ 或 10 mM 咖啡因可消除不规则的电压模式和张力。我们得出的结论是，SR 振荡器对表面膜的扰动表现出相位依赖性的敏感性。因此，外部扰动会引起自发 SR 振荡和膜电压之间的相位差，从而导致锁相或不规则电压模式。这些发现确定了一种细胞内机制，该机制可能导致细胞内 Ca2+ 超载导致心律失常的发生。
These experiments analyse the phase‐dependent properties of spontaneous oscillations of the sarcoplasmic reticulum (SR) induced by Ca2+ overload. Right atrial tissue was loaded with intracellular Ca2+ by exposure to a modified Tyrode solution containing 50% of normal Na+ and 0.5 mM K+. Verapamil (2 microM) was added to block regenerative activity. Intracellular Ca2+ overload elicited spontaneous, rhythmic voltage and tension oscillations that were phase locked 1:1. Voltage and tension oscillations were abolished by exposure to low (0.9 mM) external Ca2+, 1 microM ryanodine, or 10 mM caffeine, indicating that both voltage and tension oscillations resulted from spontaneous oscillations in SR Ca2+ release. Single pulses of nerve‐stimulated ACh release elicited phase shifts in both voltage and tension oscillations. Sinusoidal current was used as a periodic stimulus to drive membrane voltage and elicit periodic voltage oscillations. Stimulated voltage oscillations entrained spontaneous tension oscillations 1:1 in a range of frequencies close to the basic spontaneous SR oscillatory cycle length, or 2:1 at frequencies close to one‐half the spontaneous SR oscillatory cycle length. Stimulation frequencies between these two regions entrained tension oscillations in predictable fixed coupled ratios (4:3, 3:2) and resulted in Wenckeback‐like voltage patterns. Stimulation frequencies between phase‐locked regions resulted in complex coupling relationships and irregular voltage patterns. Exposure to 1 microM ryanodine, 0.9 mM external Ca2+, or 10 mM caffeine abolished irregular voltage patterns and tension. We conclude that the SR oscillator exhibits phase‐dependent sensitivity to perturbations at the surface membrane. As a result, external perturbations can elicit phase differences between spontaneous SR oscillations and membrane voltage that cause either phase‐locked or irregular voltage patterns. These findings identify an intracellular mechanism that may contribute to the development of cardiac dysrhythmias resulting from intracellular Ca2+ overload.