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dc.contributor.authorFretwell, L.en
dc.contributor.authorDickenson, J.en
dc.date.accessioned2013-04-10T10:21:40Z
dc.date.available2013-04-10T10:21:40Z
dc.date.issued2009-09-15
dc.identifier.citationFretwell, L. and Dickenson, J. (2009) Role of large-conductance Ca2+ -activated potassium channels in adenosine A1 receptor-mediated pharmacological preconditioning in H9c2. European Journal of Pharmacology, 618, pp. 37-44en
dc.identifier.urihttp://hdl.handle.net/2086/8343
dc.description.abstractLarge-conductance Ca2+-activated potassium channels, located on the inner mitochondrial membrane, have recently been implicated in cytoprotection. Therefore, the primary aim of this study was to determine the role of large-conductance Ca2+-activated potassium channels in adenosine A1 receptor-induced pharmacological preconditioning in the rat embryonic cardiomyoblast-derived cell line H9c2. For pharmacological preconditioning, H9c2 cells were exposed to the adenosine A1 receptor agonist N6-cyclopentyladenosine (100 nM) or the Ca2+-activated potassium channel opener NS1619 (10 µM) for 30 min prior to 6 h hypoxia (0.5% O2) in glucose-free and serum-free media. Where appropriate cells were treated (15 min) before pharmacological preconditioning with the Ca2+-activated potassium channels blockers paxilline (1 µM) or iberiotoxin (100 nM). Cell viability following 6 h hypoxia was assessed by monitoring lactate dehydrogenase (LDH) release and caspase-3 activation. Ca2+-activated potassium channel subunit protein expression and cell survival protein kinase (ERK1/2 and PKB/Akt) activation were assessed by Western blotting. The results demonstrate that the adenosine A1 receptor is functionally expressed in H9c2 cells and when activated protects against hypoxia-induced LDH release and caspase-3 activation. Treatment with paxilline or iberiotoxin attenuated adenosine A1 receptor and NS1619-induced pharmacological preconditioning. Large-conductance Ca2+-activated potassium channel α and β4 protein subunits were detected in mitochondrial fractions isolated from H9c2 cells. NS1619 (10 µM) induced no significant changes in ERK1/2 or PKB phosphorylation. These results have shown for the first time that large-conductance Ca2+-activated potassium channels are involved in adenosine A1 receptor-induced pharmacological preconditioning in a cell model system.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAdenosineen
dc.subjectH9c2 cellen
dc.subjectLarge-conductance Ca2+-activated potassium channelen
dc.subjectHypoxiaen
dc.subjectAdenosine A1 receptoren
dc.subjectPharmacological preconditioningen
dc.titleRole of large-conductance Ca2+ -activated potassium channels in adenosine A1 receptor-mediated pharmacological preconditioning in H9c2 cellsen
dc.typeArticleen
dc.identifier.doihttp://dx.doi.org/10.1016/j.ejphar.2009.07.008
dc.peerreviewedYesen
dc.ref2014.selected1365591152_1310680262232_3_1
dc.researchinstituteInstitute for Allied Health Sciences Researchen


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