Intracellular alkalinization induces Ca2+ influx via non-voltage-operated Ca2+ channels in rat aortic smooth muscle cells

Wakako Eto, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Hideo Kanaide

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


In smooth muscle, the cytosolic Ca2+ concentration ([Ca2+]i) is the primary determinant of contraction, and the intracellular pH (pHi) modulates contractility. Using fura-2 and 2′,7′-biscarboxyethyl-5(6) carboxyfluorescein (BCECF) fluorometry and rat aortic smooth muscle cells in primary culture, we investigated the effect of the increase in pHi on [Ca2+]i. The application of the NH4Cl induced concentration-dependent increases in both pHi and [Ca2+]i. The extent of [Ca2+]i elevation induced by 20 mM NH4Cl was approximately 50% of that obtained with 100 mM K+-depolarization. The NH4Cl-induced elevation of [Ca2+]i was completely abolished by the removal of extracellular Ca2+ or the addition of extracellular Ni2+. The 100 mM K+-induced [Ca2+]i elevation was markedly inhibited by a voltage-operated Ca2+ channel blocker, diltiazem, and partly inhibited by a non-voltage-operated Ca2+ channel blocker, SKF96365. On the other hand, the NH4Cl-induced [Ca2+]i elevation was resistant to diltiazem, but was markedly inhibited by SKF96365. It is thus concluded that intracellular alkalinization activates the Ca2+ influx via non-voltage-operated Ca2+ channels and thereby increases [Ca2+]i in the vascular smooth muscle cells. The alkalinization-induced Ca2+ influx may therefore contribute to the enhancement of contraction.

Original languageEnglish
Pages (from-to)477-484
Number of pages8
JournalCell Calcium
Issue number6
Publication statusPublished - Dec 2003

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Intracellular alkalinization induces Ca<sup>2+</sup> influx via non-voltage-operated Ca<sup>2+</sup> channels in rat aortic smooth muscle cells'. Together they form a unique fingerprint.

Cite this