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.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Harmati G,Bányász T,Bárándi L,Szentandrássy N,Horváth B,Szabó G,Szentmiklósi JA,Szénási G,Nánási PP,Magyar Jdoi
10.1111/j.1476-5381.2010.01092.xsubject
Has Abstractpub_date
2011-02-01 00:00:00pages
890-6issue
4eissn
0007-1188issn
1476-5381journal_volume
162pub_type
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