Role of large-conductance Ca2+-activated K+ channels in adenosine A1 receptor-mediated pharmacological postconditioning in H9c2 cells

Date

2011-12-21

Advisors

Journal Title

Journal ISSN

ISSN

Volume Title

Publisher

NRC Research Press

Type

Article

Peer reviewed

Abstract

Ischaemic postconditioning is a phenomenon whereby short periods of ischaemia applied during the start of reperfusion protect the myocardium from the damaging consequences of reperfusion. As such, pharmacological-induced postconditioning represents an attractive therapeutic strategy for reducing reperfusion injury during cardiac surgery and following myocardial infarction. The primary aim of this study was to determine the role of large-conductance Ca2+-activated potassium channels (BKCa channels) in adenosine A1 receptor-induced pharmacological postconditioning in the rat embryonic cardiomyoblast-derived cell line H9c2. H9c2 cells were exposed to 6 h hypoxia (0.5% O2) followed by 18 h reoxygenation (H/R) after which cell viability was assessed by monitoring lactate dehydrogenase (LDH) release and caspase-3 activation. The adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 100 nmol/L) or the BKCa channel opener NS1619 (10 µmol/L) were added for 30 min at the start of reoxygenation following 6 h hypoxic exposure. Where appropriate, cells were treated (15 min) before pharmacological postconditioning with the BKCa channel blockers paxilline (1 µmol/L) or iberiotoxin (100 nmol/L). Pharmacological postconditioning with CPA or NS1619 significantly reduced H/R-induced LDH release. Treatment with paxilline or iberiotoxin attenuated adenosine A1 receptor and NS1619-induced pharmacological postconditioning. These results have shown for the first time that BKCa channels are involved in adenosine A1 receptor-induced pharmacological postconditioning in a cell model system.

Description

Keywords

Adenosine, H9c2 cells, Large-conductance Ca2+-activated potassium channel, Hypoxia, Adenosine A1, Pharmacological postconditioning

Citation

Fretwell, L. and Dickenson, J. (2011) Role of large-conductance Ca2+-activated K+ channels in adenosine A1 receptor-mediated pharmacological postconditioning in H9c2 cells. Canadian Journal. Physiology and Pharmacology, 89 (1), pp. 24-30

Rights

Research Institute

Institute for Allied Health Sciences Research