Eisner D A, Kashimura T, Venetucci L A, Trafford A W
Manchester Academic Health Science Centre, The University of Manchester, Core Technology Facility, Manchester, UK.
Circ J. 2009 Sep;73(9):1561-7. doi: 10.1253/circj.cj-09-0478. Epub 2009 Aug 10.
Cardiac contraction is activated by an increase of intracellular calcium concentration (Ca(2+)), most of which comes from the sarcoplasmic reticulum (SR) where it is released, via the ryanodine receptor (RyR), in response to Ca(2+) entering the cell on the L-type Ca(2+) current. This phenomenon is termed Ca(2+)-induced Ca(2+) release (CICR). However, under certain circumstances, the SR can become overloaded with Ca(2+) and once a threshold SR Ca(2+) content is reached Ca(2+) is released spontaneously. Such spontaneous Ca(2+) release from the SR propagates as a Ca(2+) wave by CICR. Some of the Ca(2+) released during a wave is removed from the cell on the electrogenic Na - Ca exchanger resulting in depolarization. This is the cellular mechanism producing delayed afterdepolarizations and is common to those arrhythmias produced by digitalis toxicity and right ventricular outflow tract tachycardia. More recently it has been suggested that arrhythmogenic Ca(2+) waves can also occur if the properties of the RyR are altered, resulting in increase of RyR open probability, for example by phosphorylation. However, in this review experimental evidence will be presented to support the view that such arrhythmias still require a threshold SR Ca(2+) content to be exceeded and that this threshold is decreased by increasing RyR open probability.
心肌收缩是由细胞内钙浓度（Ca(2+)）升高激活的，其中大部分钙来自肌浆网（SR），它通过兰尼碱受体（RyR）释放，以响应通过L型钙电流进入细胞的Ca(2+)。这种现象被称为钙诱导钙释放（CICR）。然而，在某些情况下，肌浆网可能会因Ca(2+)过载，一旦达到肌浆网Ca(2+)含量阈值，Ca(2+)就会自发释放。这种来自肌浆网的自发Ca(2+)释放通过CICR以Ca(2+)波的形式传播。在一波释放过程中释放的一些Ca(2+)通过电致钠钙交换体从细胞中移除，导致去极化。这是产生延迟后去极化的细胞机制，并且在由洋地黄毒性和右心室流出道心动过速引起的心律失常中很常见。最近有人提出，如果RyR的特性发生改变，例如通过磷酸化导致RyR开放概率增加，也会发生致心律失常的Ca(2+)波。然而，在本综述中，将提供实验证据来支持这样一种观点，即这种心律失常仍然需要超过肌浆网Ca(2+)含量阈值，并且通过增加RyR开放概率会降低该阈值。
