Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes.
Cardiovasc Res
; 31(2): 237-45, 1996 Feb.
Article
em En
| MEDLINE
| ID: mdl-8730400
ABSTRACT
OBJECTIVES:
The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031.METHODS:
Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patch clamp procedure during perfusion of normotonic, normotonic with addition of E-4031, and hypotonic plus E-4031 solutions.RESULTS:
Cell swelling leading to membrane stretch of myocytes in the whole-cell recording configuration occurred with hypotonic solution perfusion. APD, prolonged by E-4031, was reduced to less than control value with hypotonic-induced stretch. Evaluation of whole-cell currents after hypotonic-induced stretch revealed no significant changes in the L-type Ca2+ current, inward rectifier K+ current or the rapid component of the delayed rectifier K+ current. The slow component of the delayed rectifier K+ current (IKs) was upregulated and a stretch-induced CI- current was activated in hypotonic solutions. The hypotonic-induced modulation of these currents was not effected by protein kinase A or C inhibition.CONCLUSIONS:
Hypotonic-induced stretch shortens APD and counteracts the effects of E-4031. This APD shortening is secondary to upregulation of IKs and activation of a stretch-induced Cl- current.
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Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Piridinas
/
Potenciais de Ação
/
Ventrículos do Coração
/
Soluções Hipotônicas
/
Antiarrítmicos
Limite:
Animals
Idioma:
En
Ano de publicação:
1996
Tipo de documento:
Article