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