Open AccessBiphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes
Author(s) -
CHENG Lufeng,
YAN Dong,
TURDI Subat,
KERRAM Parhat
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00575.x
Subject(s) - haloperidol , chemistry , guinea pig , ic50 , sodium , patch clamp , endocrinology , pharmacology , medicine , biophysics , electrophysiology , biology , biochemistry , in vitro , dopamine , organic chemistry
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 I Na in a concentration‐dependent manner with an IC 50 of 0.253±0.015 7mu;mol/L. The inhibition rate of haloperidol (0.3 μmol/L) on I Na was 22.14%± 0.02%, and the maximum conductance was reduced. Haloperidol significantly reduced the midpoints for the activation and inactiva‐ion 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 μmol/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 μmol/L haloperidol administration, indicating that the drug affects the inactivated state of sodium channels.