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STUDY OF THE ALCOHOLS INFLUENCE ON EXCITATION WAVE PROPAGATION IN NEONATAL RAT VENTRICULAR MYOCYTE MONOLAYER

Name
Alisa
Surname
Podgurskaya
Scientific organization
MIPT
Academic degree
Bachelor
Position
Master student
Scientific discipline
Life Sciences & Medicine
Topic
STUDY OF THE ALCOHOLS INFLUENCE ON EXCITATION WAVE PROPAGATION IN NEONATAL RAT VENTRICULAR MYOCYTE MONOLAYER
Abstract
Cardiac arrhythmias are often associated with alcohol consumption. However, the underlying mechanism of alcohol induced arrhythmias still poorly known. In this study we show the effect of ethanol and heptanol on excitation wave propagation on the experimental heart model - neonatal rat ventricular myocyte (NRVM) monolayer by optical mapping method.
Keywords
Optical Mapping, Arrhythmias, Reentry, Gap-junction, Ethanol
Summary

A wide range of chemical compounds and drugs has potential cardiotoxic effect which can result in cardiac arrhythmias. A special role in this case play alcohols. In medical research it is a known fact that the use of ethanol in large quantities causes cardiomyopathy and prolongs QT-interval [1]. In the experiments on isolated cells it was shown that the ethanol inhibits voltage-gated ion channels (fast sodium, L-type calcium channels and the transient outward potassium current) [2]. But a full picture of fundamental role of this substance in the cardiac functioning still does not exist. Heptanol is used in the electrophysiology as a gap junctions blocker [3,4]. In our study we put in a goal to evaluate effects of ethanol and heptanol on a cultured monolayer of cells - neonatal rat ventricular myocytes (NRVM).

While increasing concentration of the alcohol, velocity of the excitation wave propagation and maximum capture rates were measured by optical mapping method. The experimental scheme is shown on Fig. 1.

Figure 1. The experimental scheme.

For both alcohols excitation wave propagation velocity decreases exponentially at concentrations from 0.05 to 1.8 mM. In experiments with heptanol conduction block was observed at 1.8 mM, which confirms its role in cells uncoupling. Notably, that in the interval between 0.4 and 0.6 mM of heptanol velocity locally rose by 20% comparing to the current values. It may indicate the activation of specific ion channels at these concentrations. On 0.1 mM the effect of heptanol accumulation with time was observed. The activation maps of NVRM monolayer with treatment of 0.9 mM heptanol/without treatment are given on Fig.2.

Figure 2. Activation maps of NVRM monolayer. A-control, B-0.9 mM heptanol. White point in the corner corresponds to the place of stimulating electrode. Scale 38 µm.

Unlike the ethanol, at high (0.8-1.4 mM) concentrations of which, excitation wave propagation velocity dropped 5-fold times comparing to normal conditions. Therefore, the length of propagating impulse decreased considerably. Consequently, the size required for the existence of reentry become significantly smaller (Fig. 3) [5]. This fact may represent pro-arrhythmogenic action of the ethanol.

Figure 3. Activation map of NVRM monolayer with 1.4 mM ethanol treatment. Scale 12 µm.

Values ​​of maximum capture rates also reduced with the increase of ethanol concentration: at 0.8-1.4 mM more than 60%. Maximum capture rate characterizes total duration of the action potential and refractory period, so its reduction with the increase of ethanol concentration is consistent with QT-prolongation data.

References:

  1. Kupari M., Koskinen P. Alcohol, cardiac arrhythmias and sudden death //Alcohol and cardiovascular diseases. Novartis Foundation Symposium. – 1998. – Т. 216. – С. 68-79.
  2. Bébarová M. et al. Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes //Acta physiologica. – 2010. – Т. 200. – №. 4. – С. 301-314.
  3. Dhein S. Pharmacology of gap junctions in the cardiovascular system //Cardiovascular research. – 2004. – Т. 62. – №. 2. – С. 287-298.
  4. Takens-Kwak B. R. et al. Mechanism of heptanol-induced uncoupling of cardiac gap junctions: a perforated patch-clamp study //American Journal of Physiology-Cell Physiology. – 1992. – Т. 262. – №. 6. – С. C1531-C1538.
  5. Winfree A. T. Electrical turbulence in three-dimensional heart muscle //Science. – 1994. – Т. 266. – №. 5187. – С. 1003-1006.