Effect of heptanol and ethanol on excitation wave propagation in a neonatal rat ventricular myocyte monolayer

A D Podgurskaya, V A Tsvelaya, S R Frolova, I Y Kalita, N N Kudryashova, K I Agladze

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias. These substances influence sodium, calcium, and potassium channels, but the complete mechanism of action of heptanol and ethanol remains unknown. The optical mapping method was used to measure conduction velocities (CVs) in concentrations of 0.05-1.8 mM heptanol and 17-1342 mM ethanol. Heptanol was shown to slow the excitation wave significantly, and a mechanism that involves a simultaneous action on cell coupling and activation threshold was suggested. Whole-cell patch-clamp experiments showed inhibition of sodium and calcium currents at a concentration of 0.5 mM heptanol. Computer modeling was used to estimate the relative contribution of the cell uncoupling and activation threshold increase caused by heptanol. Unlike heptanol, ethanol slightly influenced the CV at clinically relevant concentrations. Additionally, the critical concentrations for re-entry formation in ethanol were determined.

Original languageEnglish
Pages (from-to)136-144
Number of pages9
JournalToxicology in Vitro
Volume51
Early online date17 May 2018
DOIs
Publication statusPublished - 1 Sept 2018
Externally publishedYes

Keywords / Materials (for Non-textual outputs)

  • Action Potentials/drug effects
  • Animals
  • Animals, Newborn
  • Ethanol/pharmacology
  • Heart Ventricles
  • Heptanol/pharmacology
  • Myocytes, Cardiac/drug effects
  • Rats, Sprague-Dawley

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