Effects of propofol on voltage-gated sodium channels and single action potention of S1 neurons in rats
1.Department of Anesthesia, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027; 2.Department of Anaesthesiology, Zunyi Medical College, Zunyi, 563003
HE Jiongce1,ZHANG Yu2,LIU Xingkui2, et al. Effects of propofol on voltage-gated sodium channels and single action potention of S1 neurons in rats[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(12): 859-.
Abstract：Objective: The aim of this study is to investigate the effects of propofol on voltage-gated sodium channels and single action potention (AP) of primary S1 neurons in rats. Methods: Brain slices were prepared from SD rats of 7 to 14 days old, and whole-cell patch clamp technique was used to record currents and voltages. After application with propofol at different concentrations (10-300 μmol/L), the sodium currents (INa) were recorded. Data were used to make current-voltage curve, steady-state activation curve, steady-state inactivation curve, deinactivation curve and account characteristic parameters. AP was activated by a 30 mspulse of 50 pA, the data of each group were taken for analysis. Results: Propofol inhibited INA of S1 neurons in rats in a dose-dependent manner (10-300 μmol/L). It also inhibited the inactivation of sodium channels, shifted the inactivation curve towards the hyperpolarzating potential, and prolonged the recovery of sodium channels from their deinactivation, however it did not affect activation of sodium channels. Propofol inhibited the overshoot of single AP of S1 neurons in rats in a dose-dependent manner (10-100 μmol/L, P<0.01), and also depressed the overshoot (100 μmol/L, P<0.01), there was no AP be activated at 300 μmol/L. Conclusion: Propofol shows an inhibitory effect on voltage-gated sodium channels and AP of S1 neurons in the thalamocortical circuit, which may play a role in the mechanisms of propofol-induced general anesthesia
[1]Kopp Lugli A, Yost CS, Kindler CH. Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia[J]. Eur J Anaesthesiol, 2009, 26(10): 807-820.
[2]Nau C. Voltage-gated ion channels[J]. Handb Exp Pharmacol, 2008, 182(1): 85-92.
[3]Alkire MT, Hudetz AG, Tononi G. Consciousness and anesthesia[J]. Science, 2008, 322(5903): 876-880.
[4]Barrett AB, Murphy M, Bruno MA, et al. Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia[J]. PLoS One, 2012, 7(1): e29072.
[5]Lingamaneni R, Hemmings HC Jr. Differential interaction of anaesthetics and antiepileptic drugs with neuronal Na+ channels, Ca2+ channels, and GABAA receptors[J]. Br J Anaesth, 2003, 90(2): 199-211.
[6]Varela F, Lachaux JP, Rodriguez E, et al. The brainweb: phase synchronization and large-scale integration[J]. Nat Rev Neurosci, 2001, 2(4): 229-239.
[7]Kimura A, Yokoi I, Imbe H, et a1. Auditory thalamic reticular nucleus of the rat: anatomicaI nodes for modulation of auditory and cross-modal sensory processing in the loop connectivity between the cortex and thalamus[J]. J Comp Neurol, 2012, 520(7): 1457-1480.
[8]曹云飞, 俞卫锋, 王士雷. 全麻原理及研究新进展[M]. 北京:人民军医出版社, 2005: 329.
[9]Pittson S, Himmel AM, Maclver MB. Multiple synapitic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices[J]. BMC Neurosci, 2004, 5: 52.
