O2 availability modulates transmembrane Ca2+ flux via second-messenger pathways in anoxia-tolerant hepatocytes
Land, S.C., Sanger, R.H. and Smith, P.J. (1997) O2 availability modulates transmembrane Ca2+ flux via second-messenger pathways in anoxia-tolerant hepatocytes. Journal of Applied Physiology, 82, (3), 776-783. (PMID:9074963).
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Transmembrane Ca(2+)-flux was studied from single isolated turtle hepatocytes by using a noninvasive Ca(2+)-selective self-referencing microelectrode. Cells in Ca(2+)-reduced culture medium demonstrated a vanadate- and lanthanum-inhibitable Ca(2+)-efflux of 4 x 10(-17) mol Ca2+. microns-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 microM. 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 microM) 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.
|Keywords:||oxygen sensing, hypometabolism, adenosine, protein kinase c, calcium homeostasis, calcium-selective self-referencing probe|
|Subjects:||Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
|Divisions:||University Structure - Pre August 2011 > Other
|Date Deposited:||17 Jun 2011 10:24|
|Last Modified:||31 Mar 2016 13:41|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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