Smooth muscle acid sensing ion channel 1: Pathophysiologic implication in hypoxic pulmonary hypertension. Academic Article Review uri icon

abstract

  • Acid sensing ion channels (ASICs) belong to the amiloride-sensitive, degenerin/epithelial sodium channel (DEG/ENaC) superfamily. ASICs are voltage-independent, proton-gated cation channels and their activity has been linked to a variety of physiological and pathological functions in the central and peripheral nervous system. Nonetheless, ASICs are expressed in a variety of tissues. In this review, we describe a novel role for ASIC1 in regulating pulmonary arterial smooth muscle cell (PASMC) Ca(2+) influx in both physiological and pathophysiological settings. Through a store-operated mechanism, ASIC1 contributes to pulmonary vasoconstriction elicited by various agonists and alveolar hypoxia. ASIC1-mediated Ca(2+) entry in PASMC is a central component to the active vasoconstriction, vascular remodeling, and right ventricular hypertrophy associated with the development of hypoxic pulmonary hypertension. Despite the requirement for ASIC1 to enhanced Ca(2+) influx in the pulmonary hypertensive circulation, these responses are not dependent on an increase in PASMC ASIC1 protein expression suggesting hypoxia promotes activation of ASIC1 through other regulatory mechanism(s). Here, we describe some of the correlations between hypoxia-induced changes in reactive oxygen species homeostasis with that of ASIC1 function. Ultimately, a better understanding of the molecular mechanisms by which ASICs are regulated will help elucidate their mechanism of action and identify potential therapeutics that specifically target ASIC. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

publication date

  • November 2014