Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle: Implications for optical measurements of cardiac repolarization

Martin Biermann, Michael Rubart, Alonso Moreno, Jiashin Wu, Avonelle Josiah-Durant, Douglas P. Zipes

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Introduction: 2,3-Butanedione monoxime (BDM) has been widely used to inhibit contraction during optical recordings of cardiac membrane voltage changes, even though it markedly abbreviates cardiac action potentials. Methods and Results: We compared the effects of BDM and of the F-actin disrupter cytochalasin D (cyto D) on isometric twitch force and transmembrane action potentials in isolated canine right ventricular trabeculae superfused with Tyrode's solution (2 mmol/L CaCl2, 37°C) and stimulated at 0.5 Hz. BDM at 10 mmol/L and cyto D at 80 μmol/L were equally effective in reducing peak isometric force to 10% ± 3% (n=6; mean±SEM) and 8% ± 1% (n=8), respectively. Neither agent significantly altered resting tension. While 10 mmol/L BDM markedly shortened the action potential duration at 90% repolarization (APD90) from 198±7 msec to 146±9 msec (P<0.001), 80 μmol/L cyto D had no significant effects on APD90 or on any other action potential parameter. The effects of BDM on peak isometric force and APD were completely reversible after 15 minutes of washout, whereas in the cyto D group contractile force continued to be reduced (13%±3%) and action potential characteristics did not show significant changes from control values after a 60-minute period of superfusion with cyto D-free Tyrode's solution. Conclusion: We conclude that cyto D should be considered an alternative excitation-contraction uncoupler for optical mapping studies of cardiac repolarization.

Original languageEnglish (US)
Pages (from-to)1348-1377
Number of pages30
JournalJournal of cardiovascular electrophysiology
Volume9
Issue number12
StatePublished - Jan 1 1998

Keywords

  • Actin
  • Butanedione monoxime
  • Cytochalasin D
  • Excitation-contraction coupling
  • Optical mapping
  • Transmembrane action potential
  • Twitch force

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

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