Show simple item record

dc.contributor.authorFretwell, L.en
dc.contributor.authorDickenson, J.en
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.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.subjectH9c2 cellen
dc.subjectLarge-conductance Ca2+-activated potassium channelen
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.researchinstituteInstitute for Allied Health Sciences Researchen

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record