TRIC(Trimeric Intracellular Cation)-A Channels Contribute to Blood Pressure Maintenance in Vascular Smooth Muscle

Abstract

TRIC (trimeric intracellular cation) channel subtypes, namely TRIC-A and TRIC-B, are intracellular monovalent cation channels postulated to mediate counter-ion movements facilitating physiological Ca(2)(+) release from intracellular stores. Tric-a-knockout mice developed hypertension during the daytime due to enhanced myogenic tone in resistance arteries. There are two Ca(2)(+) release mechanisms in vascular smooth muscle cells (VSMCs); incidental opening of ryanodine receptors (RyRs) generates local Ca(2)(+) sparks to induce hyperpolarization, while agonist-induced activation of inositol trisphosphate receptors (IP(3)Rs) evokes global Ca(2)(+) transients causing contraction. Tric-a gene ablation inhibited RyR-mediated hyperpolarization signaling to stimulate voltage-dependent Ca(2)(+) influx, and adversely enhanced IP(3)R-mediated Ca(2)(+) transients by overloading Ca(2)(+) stores in VSMCs. Therefore, TRIC-A channels contribute to maintaining blood pressure in vascular smooth muscles.