Functional Role of Na+/H+ Exchanger in Ca2+ Influx Mediated via Human Endothelin Type A Receptor Stably Expressed in Chinese Hamster Ovary Cells

Abstract

This study examines the functional role of Na+/H+ exchanger (NHE) in Ca2+ influx mediated by human endothelin type A receptor (ETAR) expressed in Chinese hamster ovary (CHO) cells. Endothelin-1 (ET-1) increased extracellular acidification rate (ECAR), which was abolished by 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an NHE inhibitor. EIPA and KB-R7943, a Na+/Ca2+ exchanger (NCX) inhibitor, inhibited ET-1-induced sustained increases in intracellular Ca2+ concentration ([Ca2+]i), and EIPA had no effect on [Ca2+]i after KB-R7943 treatment. ET-1-elicited sustained [Ca2+]i increase was suppressed by reducing extracellular Na+ concentration. These results suggest that possible coupling of NHE with NCX via Na+ transport is involved in ETAR-mediated sustained [Ca2+]i increase. Keywords:: endothelin type A receptor, Na+/H+ exchanger, intracellular free Ca2+ concentration