O2 availability modulates transmembrane Ca2+ flux via second- messenger pathways in anoxia-tolerant hepatocytes

S. C. Land, R. H. Sanger, P. J. S. Smith

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Transmembrane Ca2+-flux was studied from single isolated turtle hepatocytes by using a noninvasive Ca2+-selective self-referencing microelectrode. Cells in Ca2+-reduced culture medium demonstrated a vanadate-and lanthanum-inhibitable Ca2+-efflux of 4 x 10-17 mol Ca2+ · μm-2 · s-1 continuously over 170 h. This flux diminished with 50 nM phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator, and was reinstated on PKC deactivation with sphingosine. Progressive hypoxia resulted in a reversible suppression of Ca2+ efflux to 90% of normoxic controls with an apparent Michaelis constant for oxygen of 145 μM. PKC activation was critical in this suppression, as anaerobic administration of sphingosine caused a Ca2+ influx and cell rupture. Hypoxia was also associated with an altered pattern of adenosine-mediated control over Ca2+ efflux. Adenosine (100 μM) elevated Ca2+ efflux twofold in normoxia, but neither adenosine nor the A1-purinoreceptor antagonist 8-phenyltheophylline altered the observed anaerobic suppression. Aerobic administration of 2-10 mM KCN failed to reproduce the anaerobic suppression; however, in conjunction with 10 mM iodoacetate, complete metabolic blockade caused a Ca2+ influx and cell rupture. These observations suggest modulatory control by oxygen over transmembrane Ca2+ efflux involving second-messenger systems in the hypoxic transition.

Original languageEnglish
Pages (from-to)776-783
Number of pages8
JournalJournal of Applied Physiology
Volume82
Issue number3
DOIs
Publication statusPublished - 1 Mar 1997

Keywords

  • adenosine
  • calcium homeostasis
  • calcium-selective
  • hypometabolism
  • oxygen sensing
  • protein kinase C
  • self-referencing probe

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