The central nervous system (CNS) pericytes play an important role in brain microcirculation. Na ϩ /H ϩ exchanger isoform 1 (NHE1) has been suggested to regulate the proliferation of nonvascular cells through the regulation of intracellular pH, Na ϩ , and cell volume; however, the relationship between NHE1 and intracellular Ca 2ϩ , an essential signal of cell growth, is still not known. The aim of the present study was to elucidate the role of NHE1 in Ca 2ϩ signaling and the proliferation of

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... n CNS pericytes. The intracellular Ca 2ϩ concentration was measured by fura 2 in cultured human CNS pericytes. The cells showed spontaneous Ca 2ϩ oscillation under quasi-physiological ionic conditions. A decrease in extracellular pH or Na ϩ evoked a transient Ca 2ϩ rise followed by Ca 2ϩ oscillation, whereas an increase in pH or Na ϩ did not induce the Ca 2ϩ responses. The Ca 2ϩ oscillation was inhibited by an inhibitor of NHE in a dose-dependent manner and by knockdown of NHE1 by using RNA interference. The Ca 2ϩ oscillation was completely abolished by thapsigargin. The proliferation of pericytes was attenuated by inhibition of NHE1. These results demonstrate that NHE1 regulates Ca 2ϩ signaling via the modulation of Ca 2ϩ release from the endoplasmic reticulum, thus contributing to the regulation of proliferation in CNS pericytes. Na ϩ /H ϩ exchanger; central nervous system; cerebral ischemia; microcirculation Address for reprint requests and other correspondence: M. Kamouchi,