Role of NHE1 in calcium signaling and cell proliferation in human CNS pericytes

Kuniyuki Nakamura, Masahiro Kamouchi, Takanari Kitazono, Junya Kuroda, Ryu Matsuo, Noriko Hagiwara, Eiichi Ishikawa, Hiroaki Ooboshi, Setsuro Ibayashi, Mitsuo Iida

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)H1700-H1707
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number4
Publication statusPublished - Apr 2008

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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