医学
内质网
电压依赖性钙通道
心力衰竭
心脏病学
钙通道
内科学
药理学
心肌梗塞
钙
刺激1
细胞生物学
内分泌学
作者
K. Bhullar Sukhwinder,K. Shah Anureet,S. Dhalla Naranjan
标识
DOI:10.31083/j.rcm.2019.03.522
摘要
Effective therapy of hypertension represents a key strategy for reducing the burden of cardiovascular disease and its associated mortality. The significance of voltage dependent L-type Ca²⁺ channels to Ca²⁺ influx, and of their regulatory mechanisms in the development of heart disease, is well established. A wide variety of L-type Ca²⁺ channel inhibitors and Ca²⁺ antagonists have been found to be beneficial not only in the treatment of hypertension, but also in myocardial infarction and heart failure. Over the past two decades, another class of Ca²⁺ channel - the voltage independent store-operated Ca²⁺ channel - has been implicated in the regulation and fine tuning of Ca²⁺ entry in both cardiac and smooth muscle cells. Store-operated Ca²⁺ channels are activated by the depletion of Ca²⁺ stores within the endoplasmic/sarcoplasmic reticulum, or by low levels of cytosolic Ca²⁺, thereby facilitating agonist-induced Ca²⁺ influx. Store-operated Ca²⁺ entry through this pivotal pathway involves both stromal interaction molecule (STIM) and Orai channels. Different degrees of changes in these proteins are considered to promote Ca²⁺ entry and hence contribute to the pathogenesis of cardiovascular dysfunction. Several blockers of store-operated Ca²⁺ channels acting at the level of both STIM and Orai channels have been shown to depress Ca²⁺ influx and lower blood pressure. However, their specificity, safety, and clinical significance remain to be established. Thus, there is an ongoing challenge in the development of selective inhibitors of store-operated Ca²⁺ channels that act in vascular smooth muscles for the improved treatment of hypertension.
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