Liao Ping, Soong Tuck Wah
National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433.
J Biomed Res. 2010 May;24(3):181-6. doi: 10.1016/S1674-8301(10)60027-9.
Calcium channel blockers (CCBs) are widely used to treat cardiovascular diseases such as hypertension, angina pectoris, hypertrophic cardiomyopathy, and supraventricular tachycardia. CCBs selectively inhibit the inward flow of calcium ions through voltage-gated calcium channels, particularly Cav1.2, that are expressed in the cardiovascular system. Changes to the molecular structure of Cav1.2 channels could affect sensitivity of the channels to blockade by CCBs. Recently, extensive alternative splicing was found in Cav1.2 channels that generated wide phenotypic variations. Cardiac and smooth muscles express slightly different, but functionally important Cav1.2 splice variants. Alternative splicing could also modulate the gating properties of the channels and giving rise to different responses to inhibition by CCBs. Importantly, alternative splicing of Cav1.2 channels may play an important role to influence the outcome of many cardiovascular disorders. Therefore, the understanding of how alternative splicing impacts Cav1.2 channels pharmacology in various diseases and different organs may provide the possibility for individualized therapy with minimal side effects.
钙通道阻滞剂（CCBs）被广泛用于治疗心血管疾病，如高血压、心绞痛、肥厚型心肌病和室上性心动过速。CCBs选择性抑制钙离子通过电压门控钙通道的内流，特别是在心血管系统中表达的Cav1.2通道。Cav1.2通道分子结构的改变可能会影响通道对CCBs阻断的敏感性。最近，在Cav1.2通道中发现了广泛的可变剪接，产生了广泛的表型变异。心脏和平滑肌表达略有不同但功能重要的Cav1.2剪接变体。可变剪接还可以调节通道的门控特性，并导致对CCBs抑制的不同反应。重要的是，Cav1.2通道的可变剪接可能在影响许多心血管疾病的结局中起重要作用。因此，了解可变剪接如何影响各种疾病和不同器官中Cav1.2通道的药理学特性，可能为副作用最小的个体化治疗提供可能性。
