Effects Of Droperidol, Propofol And Ketamine On Na～+ Channels Of Rat Hippocampal Neurons

Objective:This study is to investigate the effects of droperidol, propofol, ketamine and the combined effects of propofol administered in combination with doperidol or ketamine on sodium channels in isolated rat hippocampal pyramidal neurons by using whole-cell patch-clamp techniques,. Method: Freshly isolated rat hippocampal pyramidal neurons were studied using the whole-cell patch clamp technique. Sodium currents were isolated from other voltage-gated currents and recorded by electrophysiological and pharmacological methods. Effects of droperidol, propofol, ketamine and the combined effects of propofol administered in combination with doperidol or ketamine on sodium channels were studied. And we also studied effects of drugs on kinetics of channels.Results: Sodium channels were inhibited by droperidol and propofol in reversible and dose-dependent manner. IC50s of doperidol, propofol on sodium channels were 26.01±5.08μmol/L and 44.53±3.89μmol/L respectively. Doperidol and propofol both had little effect on the activation curve of sodium channels. However droperidol caused hyperpolarizing shift of steady-state inactivation curve. Besides, propofol were adminstered in combination with different concentration of droperidol. When propofol was administered combined with 1/4 IC50 droperidol, the IC50 values for blocking sodium current were located in the 95% confidence limits of theoretical additive line. When propofol was administered combined with 3/4 IC50 droperidol, the IC50 values for blocking sodium current were located out of the 95% confidence limits of theoretical addictive line. Ketamine 0.18mmol/L had little effects on sodium current while ketamine 0.54mmol/L,1.8mmol/L,5.4mmol/L,10.8mmol/L inhibited it. IC50s of ketamine on sodium channels were 2.7±0.69mmol/L. When ketamine was adminstered in combination with 1/4 IC50 and 3/4 IC50 propofol. The IC50 values of ketamine for blocking sodium current were both located in the 95% confidence limitsof theoretical additive line. Conclusion:Droperidol, propofol and ketamine all inhibited sodium currents in a dose-dependent and reversible manner. In a clinically relevant concentration, droperidol and propofol inhibited sodium channels more than ketamine did. The block is relevant to its higher affinity for inactivate sodium channels. The interaction between small dose of doperidol and propofol on sodium currents is additive. The interaction between propofol and ketamine on sodium currents is too. Their combination may strengthen the sedative effects of propofol...