Role of action potential configuration and the contribution of C²âºa and K⺠currents to isoprenaline-induced changes in canine ventricular cells.
Br J Pharmacol
; 167(3): 599-611, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22563726
ABSTRACT
BACKGROUND AND PURPOSE:
Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²âº current (I(Ca)), slow delayed rectifier K⺠current (I(Ks)) and fast delayed rectifier K⺠current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTALAPPROACH:
Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEYRESULTS:
In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Potenciales de Acción
/
Miocitos Cardíacos
/
Canales de Potasio de Tipo Rectificador Tardío
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Isoproterenol
Límite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Hungria