IMR Press / RCM / Volume 20 / Issue 3 / DOI: 10.31083/j.rcm.2019.03.522
Open Access Review
Store-operated calcium channels: Potential target for the therapy of hypertension
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1. Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, R2H 2A6, Canada
Rev. Cardiovasc. Med. 2019 , 20(3), 139–151; https://doi.org/10.31083/j.rcm.2019.03.522
Submitted: 5 July 2019 | Accepted: 22 August 2019 | Published: 30 September 2019
Abstract

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 Ca 2+ channels to Ca 2+ 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 Ca 2+ channel - the voltage independent store-operated Ca 2+ 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 Ca 2+, thereby facilitating agonist-induced Ca 2+ influx. Store-operated Ca 2+ 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 Ca 2+ channels acting at the level of both STIM and Orai channels have been shown to depress Ca 2+ 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.

Keywords
Store-operated Ca2+-channels
endoplasmic/sarcoplasmic Ca2+ stores
stromal interaction molecule
orai channels
hypertension therapy
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