Emptying of Ca2+ stores elicits changes in cytosolic pH

R. M. Lynch, S. Murphy, W. Fraleigh

Research output: Contribution to journalArticlepeer-review


Ca2+ release from cellular stores activates vascular smooth muscle (VSM) contraction in response to many agonists. Emptying of the stores often activates Ca2+ influx across the plasmalemma. The mechanism by which store emptying activates Ca2+ influx is unclear, though evidence exists for a messenger that diffuses from the stores to activate a Ca2+ current. Ca2+ itself is not the messenger. Some Ca2+ storage compartments in VSM are acidic. We co-loaded A7R5 VSM cells with Fura-2 and Snarf-1, to simultaneously monitor cell Ca2+ and pH. Inhibition of SERCA Ca2+-ATPase by thapsigargin (TG) initiated a sustained increase in cell Ca2+ and H+. In the absence of extracellular Ca2+, TG also elicited an increase in Ca2+ and H+, but cell Ca2+ declined to basal levels within minutes. Adding Ca2+ back elicited a rapid increase in [Ca2+]i, and the increase was not inhibited by pretreatment with L-type Ca2+ channel blockers. Release of Ca2+ by elevating IP3 levels using arginine vasopressin (AVP) also induced Ca2+ release, and subsequent influx of extracellular Ca2+, however [H+]i decreased, and the magnitude of the Ca2+ influx was significantly greater if AVP was used to empty the Ca2+ stores. Addition of TG after AVP elicits cell acidification and a small release of Ca2+indicating that an AVP insensitive pool is the source of protons. We conclude that changes in H+ levels influence the magnitude of the store operated Ca2+ influx, but are not likely to be the physiologically relevant initiating diffusable messenger.

Original languageEnglish (US)
Pages (from-to)A1022
JournalFASEB Journal
Issue number5
StatePublished - Mar 20 1998

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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