The central nervous system (CNS) pericytes play an important role in brain microcirculation. Na+/H+ exchanger isoform 1 (NHE1) has been suggested to regulate the proliferation of nonvascular cells through the regulation of intracellular pH, Na+, and cell volume; however, the relationship between NHE1 and intracellular Ca2+, an essential signal of cell growth, is still not known. The aim of the present study was to elucidate the role of NHE1 in Ca2+ signaling and the proliferation of human CNS pericytes. The intracellular Ca2+ concentration was measured by fura 2 in cultured human CNS pericytes. The cells showed spontaneous Ca2+ oscillation under quasi-physiological ionic conditions. A decrease in extracellular pH or Na+ evoked a transient Ca 2+ rise followed by Ca2+ oscillation, whereas an increase in pH or Na+ did not induce the Ca2+ responses. The Ca2+ oscillation was inhibited by an inhibitor of NHE in a dose-dependent manner and by knockdown of NHE1 by using RNA interference. The Ca2+ oscillation was completely abolished by thapsigargin. The proliferation of pericytes was attenuated by inhibition of NHE1. These results demonstrate that NHE1 regulates Ca2+ signaling via the modulation of Ca2+ release from the endoplasmic reticulum, thus contributing to the regulation of proliferation in CNS pericytes.
|ジャーナル||American Journal of Physiology - Heart and Circulatory Physiology|
|出版ステータス||出版済み - 4 2008|
All Science Journal Classification (ASJC) codes