Effects of ß-adrenoceptor stimulation on delayed rectifier K(+) currents in canine ventricular cardiomyocytes.
Br J Pharmacol
; 162(4): 890-6, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-20973780
ABSTRACT
BACKGROUND AND PURPOSE:
While the slow delayed rectifier K(+) current (I(Ks)) is known to be enhanced by the stimulation of ß-adrenoceptors in several mammalian species, phosphorylation-dependent regulation of the rapid delayed rectifier K(+) current (I(Kr)) is controversial. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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 ß1-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 ß1-adrenoceptors increases I(Kr), similar to I(Ks), via the activation of PKA in canine ventricular cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Potenciais de Ação
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Receptores Adrenérgicos beta 1
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Agonistas Adrenérgicos beta
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Miócitos Cardíacos
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Canais de Potássio de Retificação Tardia
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Ventrículos do Coração
Limite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Hungria
País de publicação:
ENGLAND
/
ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM