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-von der Lohe, Alonso Moreno, Jiashin Wu, Avonelle Josiah-Durant, Douglas P. Zipes

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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
Pages (from-to)1348-1357
Number of pages10
JournalJournal of Cardiovascular Electrophysiology
Volume9
Issue number12
StatePublished - 1998

Fingerprint

Cytochalasin D
Membrane Potentials
Action Potentials
Muscles
pamidronate
diacetylmonoxime
Canidae
Actins
Membranes

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

Cite this

@article{f1a9a2ec5d1940059d16b6efa560e5ae,
title = "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",
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.",
keywords = "Actin, Butanedione monoxime, Cytochalasin D, Excitation-contraction coupling, Optical mapping, Transmembrane action potential, Twitch force",
author = "Martin Biermann and {Rubart-von der Lohe}, Michael and Alonso Moreno and Jiashin Wu and Avonelle Josiah-Durant and Zipes, {Douglas P.}",
year = "1998",
language = "English",
volume = "9",
pages = "1348--1357",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
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TY - JOUR

T1 - Differential effects of cytochalasin D and 2,3 butanedione monoxime on isometric twitch force and transmembrane action potential in isolated ventricular muscle

T2 - Implications for optical measurements of cardiac repolarization

AU - Biermann, Martin

AU - Rubart-von der Lohe, Michael

AU - Moreno, Alonso

AU - Wu, Jiashin

AU - Josiah-Durant, Avonelle

AU - Zipes, Douglas P.

PY - 1998

Y1 - 1998

N2 - 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.

AB - 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.

KW - Actin

KW - Butanedione monoxime

KW - Cytochalasin D

KW - Excitation-contraction coupling

KW - Optical mapping

KW - Transmembrane action potential

KW - Twitch force

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M3 - Article

VL - 9

SP - 1348

EP - 1357

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 12

ER -