Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes.

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.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Groh WJ,Gibson KJ,Maylie JG

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

237-45

issue

2

eissn

0008-6363

issn

1755-3245

pii

0008-6363(95)00106-9

journal_volume

31

pub_type

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