[TRIC channel and hypertension]

Abstract

TRIC channel subtypes form bullet-shaped homo-trimeric assemblies and behave as K (+) channels in intracellular membrane systems. The pathophysiological defects observed in knockout mice suggest that TRIC channels mediate counter-K (+) movements to facilitate Ca(2 +) release from intracellular stores in various cell types. In vascular smooth muscle cells (VSMCs) , Ca(2 +) release mediated by ryanodine receptors (RyRs) generates local Ca(2 +) sparks, which activate cell-surface Ca(2 +) -dependent K (+) channels and induce hyperpolarization. Tric-a-knockout mice develop hypertension due to elevated resting tonus in the mutant VSMCs. In Tric-a-knockout VSMCs, RyR-mediated Ca(2 +) sparks are compromised and the hyperpolarization signaling is thus impaired. Under such depolarized conditions, voltage-dependent L-type Ca(2 +) channels are hyper-activated to enhance resting tonus in Tric-a-knockout VSMCs. Therefore, the expression level of TRIC-A channels in VSMCs seems to set resting blood pressure at whole animal level. Moreover, our association study identified several single nucleotide polymorphisms (SNPs) around the TRIC-A gene that increase a hypertension risk and restrict the efficiency of antihypertensive drugs. The observations suggest that the TRIC-A SNPs can provide biomarkers for the diagnosis and personalized medical treatment of essential hypertension.