Dataset Information

Effects of ?-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes.

ABSTRACT:

Background and purpose

While the slow delayed rectifier K(+) current (I(Ks)) is known to be enhanced by the stimulation of ?-adrenoceptors in several mammalian species, phosphorylation-dependent regulation of the rapid delayed rectifier K(+) current (I(Kr)) is controversial.

Experimental approach

In the present study, therefore, the effect of isoprenaline (ISO), activators and inhibitors of the protein kinase A (PKA) pathway on I(Kr) and I(Ks) was studied in canine ventricular myocytes using the whole cell patch clamp technique.

Key results

I (Kr) was significantly increased (by 30-50%) following superfusion with ISO, forskolin or intracellular application of PKA activator cAMP analogues (cAMP, 8-Br-cAMP, 6-Bnz-cAMP). Inhibition of PKA by Rp-8-Br-cAMP had no effect on baseline I(Kr). The stimulating effect of ISO on I(Kr) was completely inhibited by selective ??-adrenoceptor antagonists (metoprolol and CGP-20712A), by the PKA inhibitor Rp-8-Br-cAMP and by the PKA activator cAMP analogues, but not by the EPAC activator 8-pCPT-2'-O-Me-cAMP. In comparison, I(Ks) was increased threefold by the activation of PKA (by ISO or 8-Br-cAMP), and strongly reduced by the PKA inhibitor Rp-8-Br-cAMP. The ISO-induced enhancement of I(Ks) was decreased by Rp-8-Br-cAMP and completely inhibited by 8-Br-cAMP.

Conclusions and implications

The results indicate that the stimulation of ??-adrenoceptors increases I(Kr), similar to I(Ks), via the activation of PKA in canine ventricular cells.

SUBMITTER: Harmati G

PROVIDER: S-EPMC3042199 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Effects of β-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes.

Harmati G G Bányász T T Bárándi L L Szentandrássy N N Horváth B B Szabó G G Szentmiklósi J A JA Szénási G G Nánási P P PP Magyar J J

British journal of pharmacology 20110201 4

<h4>Background and purpose</h4>While the slow delayed rectifier K(+) current (I(Ks)) is known to be enhanced by the stimulation of β-adrenoceptors in several mammalian species, phosphorylation-dependent regulation of the rapid delayed rectifier K(+) current (I(Kr)) is controversial.<h4>Experimental approach</h4>In the present study, therefore, the effect of isoprenaline (ISO), activators and inhibitors of the protein kinase A (PKA) pathway on I(Kr) and I(Ks) was studied in canine ventricular myo ...[more]

PMID: 20973780

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