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

Abstract

Background Previous studies demonstrated general anesthetics affect potassium ion channels, which may be one of the mechanisms of general anesthesia. Because the effect of etomidate on potassium channels in rat hippocampus which is involved in memory function has not been studied, we investigated the effects of etomidate on both delayed rectifier potassium current (Ik(dr)) and transient outward potassium current (Ik(a)) in acutely dissociated rat hippocampal pyramidal neurons. Methods Single rat hippocampal pyramidal neurons from male Wistar rats of 7-10 days were acutely dissociated by enzymatic 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 List EPC-10 amplifier and data were stored in a computer using Pulse 8.5. Student's paired two-tail t test was used for data analysis. Results At the concentration of 100 μmol/L, etomidate significantly inhibited Ik(dr) by 49.2% at +40 mV when depolarized from -110 mV (P <0.01, n=8), while did not affect Ik(a) (n=8, P >0.05). The IC50 value of etomidate for blocking 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 V1/2 of activation curve was shifted from (17.3±1.5) mV to (10.7±2.9) mV (n=8, P<0.05), the V1/2 of inactivation curve was shifted from (-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 and inactivation 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 inhibited by etomidate in a concentration-dependent manner, while Ik(a) remained unaffected. Chin Med J 2010;123(6):702-706