Effects of thymol on calcium and potassium currents in canine and human ventricular cardiomyocytes.
1. Concentration-dependent effects of thymol (1 - 1000 microM) 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 microM) removed the notch of the action potential, whereas high concentrations (100 microM or higher) caused an additional shortening of action potential duration accompanied by progressive depression of plateau and reduction of V(max). 3. In the canine cells L-type Ca current (I(Ca)) was decreased by thymol in a concentration-dependent manner (EC(50): 158+/-7 microM, Hill coeff.: 2.96+/-0.43). In addition, thymol (50 - 250 microM) accelerated the inactivation of I(Ca), increased the time constant of recovery from inactivation, shifted the steady-state inactivation curve of I(Ca) 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, I(to) (EC(50): 60.6+/-11.4 microM, Hill coeff.: 1.03+/-0.11), the rapid component of the delayed rectifier, I(Kr) (EC(50): 63.4+/-6.1 microM, Hill coeff.: 1.29+/-0.15), and the slow component of the delayed rectifier, I(Ks) (EC(50): 202+/-11 microM, 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.
Magyar
János
J
Department of Physiology, University Medical School of Debrecen, H-4012 Debrecen, P.O. Box 22, Hungary.
Szentandrássy
Norbert
N
Bányász
Tamás
T
Fülöp
László
L
Varró
András
A
Nánási
Péter P
PP
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D013943:Thymol / Q000494:pharmacology*; D016276:Ventricular Function
D015220:Calcium Channels; D015221:Potassium Channels; D013943:Thymol