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

• Published in: Toxicology in vitro 2018-09, Vol.51, p.136-144
• Main Authors: Podgurskaya, A.D., Tsvelaya, V.A., Frolova, S.R., Kalita, I.Y., Kudryashova, N.N., Agladze, K.I.
• Format: Article
• Language: English
• Subjects: Arrhythmia; Calcium; Calcium channels; Cardiac arrhythmia; Cardiac excitation wave; Cell activation; Channels; Conduction; Electrophysiology; Ethanol; Excitation; Heptanol; Mapping; Medical research; Monolayers; Neonates; Optical mapping; Potassium; Potassium channels; Sodium; Two dimensional models; Uncoupling; Ventricle; Wave propagation
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2018.05.009

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. •Heptanol serves both as a cell uncoupler and an inhibitor of fast sodium and L-type calcium voltage-gated ion channels•The relative contribution of both heptanol effects is estimated at different concentrations•Heptanol and ethanol decrease conduction velocity in a heart tissue•Ethanol at clinically relevant concentrations slightly influence excitation wave propagation•The critical concentrations for possible reentry formation under ethanol are found