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Store-operated calcium channels: Potential target for the therapy of hypertension.
Rev Cardiovasc Med. 2019 Sep 30; 20(3):139-151.RC

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 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.

Authors+Show Affiliations

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.Kinesiology and Nutritional Science, California State University, Los Angeles, CA, 90032, USA.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.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31601088

Citation

Bhullar, Sukhwinder K., et al. "Store-operated Calcium Channels: Potential Target for the Therapy of Hypertension." Reviews in Cardiovascular Medicine, vol. 20, no. 3, 2019, pp. 139-151.
Bhullar SK, Shah AK, Dhalla NS. Store-operated calcium channels: Potential target for the therapy of hypertension. Rev Cardiovasc Med. 2019;20(3):139-151.
Bhullar, S. K., Shah, A. K., & Dhalla, N. S. (2019). Store-operated calcium channels: Potential target for the therapy of hypertension. Reviews in Cardiovascular Medicine, 20(3), 139-151. https://doi.org/10.31083/j.rcm.2019.03.522
Bhullar SK, Shah AK, Dhalla NS. Store-operated Calcium Channels: Potential Target for the Therapy of Hypertension. Rev Cardiovasc Med. 2019 Sep 30;20(3):139-151. PubMed PMID: 31601088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Store-operated calcium channels: Potential target for the therapy of hypertension. AU - Bhullar,Sukhwinder K, AU - Shah,Anureet K, AU - Dhalla,Naranjan S, PY - 2019/07/05/received PY - 2019/08/22/accepted PY - 2019/10/12/entrez PY - 2019/10/12/pubmed PY - 2020/1/3/medline KW - Store-operated Ca²⁺-channels KW - endoplasmic/sarcoplasmic Ca²⁺ stores KW - hypertension therapy KW - orai channels KW - stromal interaction molecule SP - 139 EP - 151 JF - Reviews in cardiovascular medicine JO - Rev Cardiovasc Med VL - 20 IS - 3 N2 - 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. SN - 1530-6550 UR - https://www.unboundmedicine.com/medline/citation/31601088/Store_operated_calcium_channels:_Potential_target_for_the_therapy_of_hypertension_ L2 - https://rcm.imrpress.com/EN/10.31083/j.rcm.2019.03.522 DB - PRIME DP - Unbound Medicine ER -