Díaz Mary E, O'Neill Stephen C, Eisner David A
Unit of Cardiac Physiology, School of Medicine, University of Manchester, UK.
Circ Res. 2004 Mar 19;94(5):650-6. doi: 10.1161/01.RES.0000119923.64774.72. Epub 2004 Jan 29.
The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca(2+) transient (Ca(2+) alternans) is due to changes of sarcoplasmic reticulum (SR) Ca(2+) content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca(2+) content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca(2+) transient. Confocal measurements showed that the larger transients resulted from propagation of Ca(2+) waves. SR Ca(2+) content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca(2+) transient amplitude. After a large transient, if SR Ca(2+) content was elevated by brief exposure of the cell to a Na(+)-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca(2+) content are sufficient to produce alternans. The dependence of Ca(2+) transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca(2+) efflux from the cell was also a steeper function of SR Ca(2+) content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca(2+) content. In conclusion, alternans of systolic Ca(2+) appears to depend on alternation of SR Ca(2+) content. This, in turn results from the steep dependence on SR Ca(2+) content of Ca(2+) release and therefore Ca(2+) efflux from the cell as a consequence of wave propagation.
这项工作的目的是研究收缩期Ca(2+)瞬变幅度的逐搏交替（Ca(2+)交替现象）是否源于肌浆网（SR）Ca(2+)含量的变化，如果是，这种交替现象是否由于控制SR Ca(2+)含量的反馈增益变化而产生。我们发现，在大鼠心室肌细胞中，用小的（20 mV）去极化脉冲刺激会产生Ca(2+)瞬变幅度的交替现象。共聚焦测量表明，较大的瞬变是由Ca(2+)波的传播引起的。SR Ca(2+)含量（通过咖啡因诱发的膜电流测量）与Ca(2+)瞬变幅度的交替现象同相交替。在一个大的瞬变之后，如果通过将细胞短暂暴露于无钠溶液中来提高SR Ca(2+)含量，那么交替现象就会中断，下一个瞬变也会很大。这表明SR Ca(2+)含量的变化足以产生交替现象。与对照条件相比，交替状态下Ca(2+)瞬变幅度对SR含量的依赖性更强。在交替过程中，细胞的Ca(2+)外流对SR Ca(2+)含量的依赖性也比对照时更强。我们将这些更强的关系归因于这样一个事实，即交替现象中较大的反应依赖于波的传播，并且波的传播是SR Ca(2+)含量的陡峭函数。总之，收缩期Ca(2+)的交替现象似乎依赖于SR Ca(2+)含量的交替。反过来，这是由于Ca(2+)释放对SR Ca(2+)含量的陡峭依赖性，以及因此作为波传播结果的细胞Ca(2+)外流。
