Trimeric intracellular cation (TRIC) channel subtypes, namely TRIC-A and TRIC-B, function as intracellular channels conducting monovalent cations throughout tissues and probably mediate counter-ion movements coupled with Ca2+ release from the endo/sarcoplasmic reticulum. Knockout mice lacking both TRIC-A and TRIC-B channels suffer embryonic cardiac failure, and the mutant cardiomyocytes display severe dysfunction in SR Ca2+ handling (Yazawa et al., Nature, 2007). In knockout mice lacking TRIC-B channels with neonatal lethality due to respiratory failure, alveolar epithelial cells exhibit compromised Ca2+ release and thus insufficiently produce and secret surfactant phospholipids (Yamazaki et al., Development, 2009). The observations indicate that TRIC channels act as counter-ion channels functionally coupled with Ca2+ release in various cell types.Here we report the direct linkage of TRIC channels with hypertension. Knockout mice lacking TRIC-A channels showed significant hypertension and bradycardia. Ca2+ channel antagonists, but not blockers for vasoactive agents, exerted antihypertensive effects in the mutant mice. Moreover, despite retaining normal passive diameters in a Ca2+-free bathing solution, the mutant arteries showed narrow diameter results from higher resting Ca2+ level maintained by Ca2+ influx via L-type Ca2+ channel. In vascular smooth muscle cells (VSMCs), spontaneous opening of ryanodine receptor channels generates local Ca2+ release called Ca2+ sparks, activates cell-surface Ca2+-dependent K+ channels and reduces membrane potential toward relaxation. Our physiological and pharmacological studies suggested that the loss of TRIC-A channels compromises Ca2+ spark and spontaneous transient outward currents (STOCs) generation. In membrane potential monitoring using the voltage-dependent dye, the mutant VSMCs exhibited elevated resting membrane potential and prolonged repolarizing phases after high KCl-induced depolarization. These results suggested that the loss of TRIC-A in VSMCs enhanced the basal tonus induced by higher resting Ca2+ level results from decrease of Ca2+ sparks, STOCs frequency and depolarization of membrane potential.