Effects of β-adrenoceptor Stimulation on Delayed Rectifier K(+) Currents in Canine Ventricular Cardiomyocytes

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2010 Oct 27

PMID 20973780

Citations 19

Authors

G Harmati

T Banyasz

L Barandi

N Szentandrassy

B Horvath

G Szabo

J A Szentmiklosi

G Szenasi

P P Nanasi

J Magyar

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: 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.

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 β₁-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 β₁-adrenoceptors increases I(Kr), similar to I(Ks), via the activation of PKA in canine ventricular cells.

Citing Articles

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Characterization and functional role of rapid- and slow-activating delayed rectifier K currents in atrioventricular node cells of guinea pigs.

Yuasa M, Kojima A, Mi X, Ding W, Omatsu-Kanbe M, Kitagawa H Pflugers Arch. 2021; 473(12):1885-1898.

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Analyzing the Role of Repolarization Gradients in Post-infarct Ventricular Tachycardia Dynamics Using Patient-Specific Computational Heart Models.

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Specific protein kinase C isoform exerts chronic inhibition on the slowly activating delayed-rectifier potassium current by affecting channel trafficking.

Gou X, Hu T, Gou Y, Li C, Yi M, Jia M Channels (Austin). 2021; 15(1):262-272.

PMID: 33535882 PMC: 7872027. DOI: 10.1080/19336950.2021.1882112.

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