Cytosolic free calcium regulation in response to acute changes in intracellular pH in vascular smooth muscle

D. C. Batlle*, R. Peces, M. S. LaPointe, M. Ye, J. T. Daugirdas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations


This study examined the mechanisms whereby alterations of intracellular pH (pH(i)) impact on free cytosolic calcium (Ca(i)/2+) in cultured rat aortic vascular smooth muscle cells (VSMC) assayed in the presence of HCO3/CO2. Rapid cell alkalinization, effected by the exposure to NH4Cl or removal of CO2 from the superfusate, produced a rapid increase in Ca(i)/2+. The rise in Ca(i)/2+ was markedly diminished when sarcoplasmic reticulum (SR) Ca2+ stores had been depleted by prior exposure to arginine vasopressin (AVP) in Ca2+-free media or when SR release and reuptake of Ca2+ were blocked by the addition of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), but was unaffected by the removal of external Ca2+ or inhibition of Ca2+ entry using NiCl2. Cell acidification also resulted in a rapid increase in Ca(i)/2+. This Ca(i)/2+ increase was most apparent when pH(i) was very low (<6.6) and was unaffected by removal of external Ca2+ or NiCl2 addition. Unlike the effect of cell alkalinization, the increase in Ca(i)/2+ associated with cell acidification was not prevented by pretreatment with AVP or TMB-8. We conclude that, in cultured VSMC, acute intracellular alkalinization and, to a lesser extent, acidification result in release of Ca2+ from internal stores. Alkalinization increases Ca(i)/2+ by promoting its release from a store which is AVP and TMB-8 sensitive, most likely the SR. Cell acidification increases Ca(i)/2+ from an intracellular store(s) that is neither AVP nor TMB-8 sensitive. The increase in Ca(i)/2+ produced by cell acidification may be explained on the basis of cell buffering such that, as cytosolic H+ increases, it displaces Ca(i)/2+ from internal buffers with similar affinities for Ca2+ and H+.

Original languageEnglish (US)
Pages (from-to)C932-C943
JournalAmerican Journal of Physiology - Cell Physiology
Issue number4 33-4
StatePublished - 1993


  • calcium buffers
  • hydrogen buffers
  • intracellular calcium release
  • sarcoplasmic reticulum
  • sodium-calcium exchange

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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