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

Toxicology in Vitro : an International Journal Published in Association with BIBRA
A D PodgurskayaKonstantin I Agladze

Abstract

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 deter...Continue Reading

Citations

Jun 22, 2019·Scientific Reports·Chandan K NagarajuKarin R Sipido
Apr 22, 2020·Annals of Biomedical Engineering·Viktor A BalashovKonstantin I Agladze

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