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J. physiol. biochem ; 73(2): 167-174, mayo 2017. graf
Artigo em Inglês | IBECS | ID: ibc-168473

RESUMO

Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10-5 M) in the presence of selective M2 antagonist methoctramine (10-7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10-8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents Ito, IKur, and IKir. In the absence of M2 blocker methoctramine, pilocarpine (10-5 M) produced stronger attenuation of ICaL and induced an increase in IKir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10-6 M) and therefore was identified as IKACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of ICaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of IKACh (AU)


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Assuntos
Animais , Camundongos , Ratos , Canais de Cálcio Tipo L/metabolismo , Regulação para Baixo , Átrios do Coração/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Receptor Muscarínico M3/metabolismo , Fenômenos Fisiológicos Celulares , Fármacos Cardiovasculares/farmacologia , Colinérgicos/farmacologia , Potenciais de Ação , Bloqueadores dos Canais de Potássio/farmacologia , Técnicas de Patch-Clamp , Microeletrodos , Técnicas In Vitro , Escina/farmacologia , Fenômenos Eletrofisiológicos
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