TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance

SummaryTRIC 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.

► 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