Anderson M E
Department of Cardiovascular Medicine, Vanderbilt University Medical School, Nashville, TN, USA.
J Intern Med. 2006 Jan;259(1):81-90. doi: 10.1111/j.1365-2796.2005.01580.x.
QT interval prolongation is incontrovertibly linked to increased risk of arrhythmias but, paradoxically, QT interval prolongation can also be an effective antiarrhythmic strategy and is in fact the goal of class III antiarrhythmic drugs. This discussion examines the cellular effects of QT interval prolongation and proposes that calmodulin kinase II (CaMKII) is a specific cellular proarrhythmic signal that is activated downstream to QT interval prolongation. Inhibition of CaMKII can prevent cellular arrhythmia surrogates and in vivo arrhythmias linked to excessive action potential prolongation, suggesting that QT interval prolongation alone does not fully account for proarrhythmia. This reasoning points to the conclusion that QT interval modulation and prolongation not only grades cellular Ca2+ entry for cardiac contraction but also has the potential to recruit Ca2+-activated signalling molecules. CaMKII is one of these molecules and CaMKII activity is at least partially responsible for the proarrhythmic consequences of excessive QT interval prolongation.
QT间期延长与心律失常风险增加无疑相关，但矛盾的是，QT间期延长也可能是一种有效的抗心律失常策略，实际上这也是III类抗心律失常药物的目标。本讨论探讨了QT间期延长的细胞效应，并提出钙调蛋白激酶II（CaMKII）是一种特定的细胞促心律失常信号，在QT间期延长后被激活。抑制CaMKII可预防细胞心律失常替代指标以及与动作电位过度延长相关的体内心律失常，这表明单纯的QT间期延长并不能完全解释促心律失常现象。这一推理得出的结论是，QT间期的调节和延长不仅为心脏收缩分级细胞Ca2+内流，还具有招募Ca2+激活信号分子的潜力。CaMKII就是其中之一，CaMKII活性至少部分导致了QT间期过度延长的促心律失常后果。
