Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons

Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one ofthe mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampuswhich is involved in memory function has not been studied, we investigated the effects of etomidate on both delayedrectifier potassium current (Ik(dr))) and transient outward potassium current (Ik(a))) in acutely dissociated rat hippocampalpyramidal neurons.Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated byenzymatic digestion and mechanical dispersion according to the methods of Kay and Wong with slight modification.Voltage-clamp recordings were performed in the whole-cell patch clamp configuration. Currents were recorded with a ListEPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student’s paired two-tail t test was used for dataanalysis.Results At the concentration of 100 μmol/L, etomidate significantly inhibited Ik(dr)) by 49.2% at +40 mV whendepolarized from -110 mV (P <0.01, n=8), while did not affect Ik(a)) (n=8, P >0.05). The ICvalue of etomidate forblocking IK(dr)) was calculated as 5.4 μmol/L, with a Hill slope of 2.45. At the presence of 10 μmol/L etomidate, the Vofactivation curve was shifted from (17.3±1.5) mV to (10.7±2.9) mV (n=8, P<0.05), the Vof inactivation curve was shiftedfrom (-18.3±2.2) mV to (-45.3+9.4) mV (n=8, P <0.05). Etomidate 10 μmol/L shifted both the activation curve andinactivation curve of IK(dr)) to negative potential, but mainly affected the inactivation kinetics.Conclusions Etomidate potently inhibited Ik(dr)) but not Ik(a)) in rat hippocampal pyramidal neurons. Ik(dr)) was inhibitedby etomidate in a concentration-dependent manner, while Ik(a)) remained unaffected.