Cell Metabolism
Volume 14, Issue 2, 3 August 2011, Pages 231-241
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Article
TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance

https://doi.org/10.1016/j.cmet.2011.05.011Get rights and content
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Summary

TRIC channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca2+ release from internal stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca2+ release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca2+ sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP3Rs) evokes global Ca2+ transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca2+ influx, and adversely enhanced IP3R-mediated Ca2+ transients by overloading Ca2+ stores in VSMCs. Moreover, association analysis identified single-nucleotide polymorphisms (SNPs) around the human TRIC-A gene that increase hypertension risk and restrict the efficiency of antihypertensive drugs. Therefore, TRIC-A channels contribute to maintaining blood pressure, while TRIC-A SNPs could provide biomarkers for constitutional diagnosis and personalized medical treatment of essential hypertension.

Highlights

► TRIC-A-knockout mice show hypertension ► TRIC-A plays an important role in hyperpolarization signaling in VSMCs ► TRIC-A genetic polymorphisms are associated with essential hypertension ► The polymorphisms restrict the efficiency of common antihypertensive drugs

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