Concentration-dependent (10-1000 μM) effects of terpenoid phenol derivatives were studied on L-type Ca2+ current in isolated canine and human ventricular cardiomyocytes using the whole-cell configuration of patch clamp technique. Carvacrol, thymol and eugenol suppressed peak Ca 2+ current at +5 mV, having EC50 values and Hill coefficients of 98±11, 158±7 and 187±15 μM and 1.42±0.05, 2.96±0.43 and 1.6±0.1, respectively, in canine myocytes. Zingerone displayed a weak effect (estimated EC50: 2±0.37 mM, Hill coefficient: 0.73±0.07), while vanillin and guaiacol failed to substantially modify Ca2+ current up to the concentration of 1 mM. In addition to tonic block, thymol and carvacrol, but not eugenol, evoked marked rate-dependent block at 2 Hz. Carvacrol and eugenol accelerated inactivation of Ca2+ current and caused leftward shift in the voltage dependence of steady-state inactivation without altering activation kinetics. Carvacrol, but not eugenol, increased the time constant of recovery from inactivation. These effects of carvacrol and eugenol developed rapidly and were largely reversible. In myocytes isolated from undiseased human hearts, the effect of carvacrol was similar to that observed in canine cells. It is concluded that suppression of cardiac Ca2+ currents by phenol derivatives is influenced by the substituent in the benzene ring, and the blocking effect of these drugs may involve interactions with the inactivation machinery of the channel.
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