Effects of midazolam on macroscopic voltage-gated potassium currents in rat sympathetic neurons / 中国临床药理学与治疗学

ABSTRACT

AIM: To explore the influence of different concentration midazolam on the macroscopic voltage gated potassium currents and to discuss the relationship between potassium currents and inhibitory effect of clinical relevant concentration midazolam on sympathetic nervous system. METHODS: Superior sympathetic ganglion neurons were dissociated enzymatically from 7 to10 day old rat. Experiments were performed about 5 h after plating at room temperature (20- 24 ℃ ). Appropriate solution was chosen to separate the K + current from the other transmembrane currents. 1 ?mol?L -1 TTX was applied to the extracelluar solution to block the Na + current. Midazolam was also resolved in extracelluar solution to get various concentration ( 0.1 , 0.3 ,3,10,50,100 ?mol?L -1 ). Currents were recorded with the patch clamp technique in whole cell configuration using glass electrodes with a tip resistance of 2- 4 M . Potassium currents were evoked by test pulse from -100 mV to +30 mV with holding potential -80mV. Data were analyzed using Clampfit 6.0 and Oringih 5.0 software. Whole cell current records were corrected for leakage and capacitance by using the P/5 protocol. RESULTS: Midazolam dose dependently inhibited the whole cell potassium currents. Clinical relevant concentration midazolam ( 0.3 ?mol?L -1 ) only reduced the peak currents by 3.89 %(P= 0.88 ). The concentration required to produce 50% current inhibition(IC 50 ) was 76.065 ?mol?L -1 . CONCLUSION: Midazolam inhibits the whole cell potassium current significantly and dose dependently, but clinical relevant concentration midazolam has minor effect on the potassium currents, indicating that the inhibitory effect of midazolam on potassium current is not related to the suppression of activity of sympathetic system.