Effects of thymol on calcium and potassium currents in canine and human ventricular cardiomyocytes

Abstract

1. Concentration-dependent effects of thymol (1-1000 μM) was studied on action potential configuration and ionic currents in isolated canine ventricular cardiomyocytes using conventional microelectrode and patch clamp techniques. 2. Low concentration of thymol (10 μM) removed the notch of the action potential, whereas high concentrations (100 μm or higher) caused an additional shortening of action potential duration accompanied by progressive depression of plateau and reduction of Vmax. 3. In the canine cells L-type Ca current (ICa) was decreased by thymol in a concentration-dependent manner (EC50: 158±7 μM, Hill coeff.: 2.96±0.43). In addition, thymol (50-250 μM) accelerated the inactivation of ICa, increased the time constant of recovery from inactivation, shifted the steady-state inactivation curve of ICa leftwards, but voltage dependence of activation remained unaltered. Qualitatively similar results were obtained with thymol in ventricular myocytes isolated from healthy human hearts. 4. Thymol displayed concentration-dependent suppressive effects on potassium currents: the transient outward current, Ito (EC50: 60.6±11.4 μM, Hill coeff.: 1.03±0.11), the rapid component of the delayed rectifier, IKr (Er50: 63.4±6.1 μM, Hill coeff.: 1.29±0.15), and the slow component of the delayed rectifier, IKs (EC50: 202±11 μm, Hill coeff.: 0.72±0.14), however, K channel kinetics were not much altered by thymol. These effects on Ca and K currents developed rapidly (within 0.5 min) and were readily reversible. 5. In conclusion, thymol suppressed cardiac ionic channels in a concentration-dependent manner, however, both drug-sensitivities as well as the mechanism of action seems to be different when blocking calcium and potassium channels.