Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

Aim: To study the effects of haloperidol on sodium currents (I-Na) in guinea pig ventricular myocytes. Method: Whole-cell patch clamp technique was employed to evaluate the effects of haloperidol on I-Na in individual ventricular myocytes. Results: Haloperidol (0.1-3 mu mol/L) inhibited I-Na in a concentration-dependent manner with an IC50 of 0.253 +/- 0.015 7 mu mol/L. The inhibition rate of haloperidol (0.3 mu mol/L) on I-Na was 22.14% +/- 0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactivation of I-Na by 2.09 and 4.09 mV, respectively. The time constant of recovery was increased. The increase in time intervals could only recover by 90.14%+/- 1.4% (n=6); however, haloperidol at 0.03 mu mol/L enhanced I-Na conductance. The midpoints for the activation and inactivation of I-Na were shifted by 1.38 and 5.69 mV, respectively, at this concentration of haloperidol. Conclusion: Haloperidol displayed a biphasic effect on I-Na in guinea pig cardiac myocytes. High concentrations of haloperidol inhibited I-Na, while lower concentrations of haloperidol shifted the activation and inactivation curve to the left. Full recovery of recovery curve was not achieved after 0.3 mu mol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.