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

William J. Groh, Kevin J. Gibson, James G. Maylie

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 (I(Ks)) 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 I(Ks) and activation of a stretch-induced Cl- current.

Original languageEnglish (US)
Pages (from-to)237-245
Number of pages9
JournalCardiovascular research
Volume31
Issue number2
DOIs
StatePublished - Feb 1 1996

Keywords

  • Antiarrhythmic drugs
  • Chloride channels
  • E-4031
  • Guinea pig ventricular myocytes
  • Membrane potential
  • Potassium channels
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Hypotonic-induced stretch counteracts the efficacy of the class III antiarrhythmic agent E-4031 in guinea pig myocytes'. Together they form a unique fingerprint.

Cite this