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

Abstract

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 μmol/L) inhibited INa in a concentration-dependent manner with an IC50 of 0.253±0.015 7mu;mol/L. The inhibition rate of haloperidol (0.3 μmol/L) on INa was 22.14% ± 0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactiva-ion of INa 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 μmol/L enhanced INa conductance. The midpoints for the activation and inactivation of INa were shifted by 1.38 and 5.69 mV, respectively, at this concentration of haloperidol. Conclusion: Haloperidol displayed a biphasic effect on INa in guinea pig cardiac myocytes. High concentrations of haloperidol inhibited INa, 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 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels. © 2007 CPS and SIMM.