title: [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.
authors.affiliation: Kyoto University, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Yamazaki
authors.forename: Shengchen
authors.initials: S
authors.lastname: Tao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: D007473:Ion Channels; D002118:Calcium