Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

Aim: Even though alcohol intoxication is often linked to arrhythmias, data describing ethanol effect on cardiac ionic channels are rare. In addition, ethanol is used as a solvent of hydrophobic compounds in experimental studies. We investigated changes of the action potential (AP) configuration and main ionic membrane currents in rat cardiomyocytes under 20–1500 mm ethanol. Methods: Experiments were performed on enzymatically isolated rat right ventricular myocytes using the whole cell patch-clamp technique at room temperature. Results: Ethanol reversibly decelerated the upstroke velocity and decreased AP amplitude and duration at 0.2 and 3 Hz. The fast sodium current I_Na, l -type calcium current I_Ca and transient outward potassium current I_to were reversibly inhibited in a concentration-dependent manner (50% inhibition at 446 ± 12, 553 ± 49 and 1954 ± 234 mm , respectively, with corresponding Hill coefficients 3.1 ± 0.3, 1.1 ± 0.2 and 0.9 ± 0.1). Suppression of I_Na and I_Ca magnitude was slightly voltage dependent. The effect on I_Ca and I_to was manifested mainly as an acceleration of their apparent inactivations with a decreased slow and fast time constant respectively. As a consequence of marked differences in n_H, sensitivity of the currents to ethanol at 10% inhibition decreases in the following order: I_Ca (75 mm , 3.5‰), I_to (170 mm , 7.8‰) and I_Na (220 mm , 10.1‰). Conclusion: Our results suggest a slight inhibition of all the currents at ethanol concentrations relevant to deep alcohol intoxication. The concentration dependence measured over a wide range may serve as a guideline when using ethanol as a solvent.