O2 availability modulates transmembrane Ca2+ flux via second-messenger pathways in anoxia-tolerant hepatocytes
O2 availability modulates transmembrane Ca2+ flux via second-messenger pathways in anoxia-tolerant hepatocytes
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.
oxygen sensing, hypometabolism, adenosine, protein kinase c, calcium homeostasis, calcium-selective self-referencing probe
776-783
Land, S.C.
ab28350f-9bd5-4f11-a1c1-ee8164fa22b8
Sanger, R.H.
ec3d4693-8abe-4cd0-89c0-02f44ebb056b
Smith, P.J.
003de469-9420-4f12-8f0e-8e8d76d28d6c
March 1997
Land, S.C.
ab28350f-9bd5-4f11-a1c1-ee8164fa22b8
Sanger, R.H.
ec3d4693-8abe-4cd0-89c0-02f44ebb056b
Smith, P.J.
003de469-9420-4f12-8f0e-8e8d76d28d6c
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), .
(PMID:9074963)
Abstract
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.
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Published date: March 1997
Keywords:
oxygen sensing, hypometabolism, adenosine, protein kinase c, calcium homeostasis, calcium-selective self-referencing probe
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Local EPrints ID: 190249
URI: http://eprints.soton.ac.uk/id/eprint/190249
ISSN: 8750-7587
PURE UUID: 146fb80d-e01d-4b8a-b62e-b0f69a8fc427
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Date deposited: 17 Jun 2011 10:24
Last modified: 15 Mar 2024 03:38
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Author:
S.C. Land
Author:
R.H. Sanger
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