Functional coupling of ET_A rceptor with Ca²⁺ -permeable nonselective cation channel

Abstract

Endothelin-1 (ET-1) induces persistent vasoconstriction via sustained increase in intracellular free Ca²⁺ concentrations ([Ca²⁺]i). Mechanisms of the elevation of [Ca²⁺]i operating at physiologically low concentrations of ET-1 are controversial. Here we report that both native ET_A receptors in vascular smooth muscle cells (VSMCs) and recombinant ET_A receptors expressed in mouse fibroblasts (Ltk^- cells) are functionally coupled with nonselective cation channel, which is permeable to Ca²⁺ and blocked by mefenamic acid. The channel is persistently activated by a low concentration of ET-1 (10^-10 M) without stimulation of inositol trisphosphates (IP₃) formation and mediates sustained vasoconstriction.