Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center Hamburg, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
J Clin Invest. 2010 Dec;120(12):4197-203. doi: 10.1172/JCI45251. Epub 2010 Nov 22.
In situations of stress the heart beats faster and stronger. According to Marks and colleagues, this response is, to a large extent, the consequence of facilitated Ca²+ release from intracellular Ca²+ stores via ryanodine receptor 2 (RyR2), thought to be due to catecholamine-induced increases in RyR2 phosphorylation at serine 2808 (S2808). If catecholamine stimulation is sustained (for example, as occurs in heart failure), RyR2 becomes hyperphosphorylated and "leaky," leading to arrhythmias and other pathology. This "leaky RyR2 hypothesis" is highly controversial. In this issue of the JCI, Marks and colleagues report on two new mouse lines with mutations in S2808 that provide strong evidence supporting their theory. Moreover, the experiments revealed an influence of redox modifications of RyR2 that may account for some discrepancies in the field.
在应激情况下，心跳会加快且更强。根据马克斯及其同事的观点，这种反应在很大程度上是由于肌质网 Ca²+释放通道 2（ryanodine receptor 2，RyR2）促进了细胞内 Ca²+释放的结果，这种促进作用被认为是由于儿茶酚胺诱导的 RyR2 在丝氨酸 2808 处的磷酸化（serine 2808，S2808）增加所致。如果儿茶酚胺刺激持续存在（例如，心力衰竭时），RyR2 会过度磷酸化并变得“渗漏”，导致心律失常和其他病理变化。这种“渗漏的 RyR2 假说”极具争议性。在本期 JCI 中，马克斯及其同事报告了两种具有 S2808 突变的新型小鼠品系，这些突变提供了有力的证据支持他们的理论。此外，这些实验还揭示了 RyR2 的氧化还原修饰的影响，这可能解释了该领域的一些差异。
