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 (ET_AR) 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 ET_AR-mediated sustained [Ca²⁺]_i increase.