关键词: 地西泮, 交感神经节, 钠通道, 膜片钳

Abstract: Aim The effects of diazepam on the whole-cell sodium currents in rat sympathetic ganglion neurons were studied to investigate the mechanisms by diazepam mediates hypotension. Methods Whole-cell patchclamp recordings were performed on enzymatically isolated rat superior cervical sympathetic gang lion neurons. Results Diazepam dose-dependently blocked the whole-cell sodium currents. Under a V_t of 0 mV and a V_h of 80 mV 0.3 μmol·L^-1 diazepam reduced sodium peak currents by 14.76 %(P <0.01), with a mean IC₅₀ values of 6.06 μmol·L^-1 (r =0.99, P <0.01); The blockade was also potential- dependent (P <0.05), under a holding potent ial of 60 mV, the mean IC₅₀ value was 4.60μmol·L^-1, 3.0 μmol·L^-1 diazepam reduced the peak values of IV curve by 48.94 % and caused 10 mV shift of I-V curve to depolarized potentials, a 0.89 mV shift of voltage-dependent activation curve to depolarized potentials (P <0.05) and a 20.12 mV shift of the steady-state inactivation curve to more hyperpolarized potentials (P <0.01). Following diazepam administration, the conditioning pulse potential at which half-maximal channels were inactivated (V_1/2), was changed from -64.13 mV to -84.25 mV and the test potential at which half-maximal channels were activated (V_1/2), was changed from -24.64 mV to -23.75 mV. Conclusion Clinically relevant concentration of diazepam has a significant inhibition on sympathetic ganglion neurons. This inhibition is dose-dependent and potential-dependent and relevant to the inactivation of sodium channel. The circulation depression of diazepam may be relevant to the direct suppression of sympathetic ganglion neurons.

Key words: diazepam, sympathetic ganglion, sodium channel, patch-clamp