Electrophysiological actions of cyclosporin A and tacrolimus on rat hippocampal CA1 pyramidal neurons  

作　　者：Yong YU Xue-qin CHEN Yao-yuan CUI Guo-yuan HU 

机构地区：[1]Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2007年第12期1891-1897,共7页中国药理学报（英文版）

基　　金：Project partly supported by a grant from the National Natural Science Foundation of China(№ 30472086)

摘　　要：Aim： The aim of the present study was to investigate the electrophysiological actions of cyclosporin A （CsA） and tacrolimus （FK506） on neurons in the brain, and to elucidate the relevant mechanisms. Methods： Whole-cell current-clamp recording was made in CA1 pyramidal neurons in rat hippocampal slices; whole- cell voltage-clamp recording was made in dissociated hippocampal CA1 pyrami- dal neurons of rats. Results： CsA （100 prnol/L） and FK506 （50 prnol/L） did not significantly alter the passive electrical properties of hippocampal CA 1 pyramidal neurons, but slowed down the repolarizing phase of the action potential. CsA （10-100 lamol/L） selectively inhibited the delayed rectifier K~ current （IK） in a concentration-dependent manner. CsA did not affect the kinetic properties of IX. Intracellular dialysis of CsA （100 prnol/L） had no effect on Ix. The inhibition ofIK by CsA （100 lamol/L） persisted under the low Ca^2＋ conditions that blocked the basal activity of calcineurin. Conclusion： CsA exerted calcineurin-independent inhibition on the Ix in rat hippocampal pyramidal neurons. Taken together with our previous finding with FK506, it is conceivable that the spike broadening caused by the immunosuppressant drugs is due to direct inhibition on the Ix.Aim： The aim of the present study was to investigate the electrophysiological actions of cyclosporin A （CsA） and tacrolimus （FK506） on neurons in the brain, and to elucidate the relevant mechanisms. Methods： Whole-cell current-clamp recording was made in CA1 pyramidal neurons in rat hippocampal slices; whole- cell voltage-clamp recording was made in dissociated hippocampal CA1 pyrami- dal neurons of rats. Results： CsA （100 prnol/L） and FK506 （50 prnol/L） did not significantly alter the passive electrical properties of hippocampal CA 1 pyramidal neurons, but slowed down the repolarizing phase of the action potential. CsA （10-100 lamol/L） selectively inhibited the delayed rectifier K~ current （IK） in a concentration-dependent manner. CsA did not affect the kinetic properties of IX. Intracellular dialysis of CsA （100 prnol/L） had no effect on Ix. The inhibition ofIK by CsA （100 lamol/L） persisted under the low Ca^2＋ conditions that blocked the basal activity of calcineurin. Conclusion： CsA exerted calcineurin-independent inhibition on the Ix in rat hippocampal pyramidal neurons. Taken together with our previous finding with FK506, it is conceivable that the spike broadening caused by the immunosuppressant drugs is due to direct inhibition on the Ix.

关 键 词：action potential CALCINEURIN cyclosporin A delayed rectifier K＋ channel HIPPOCAMPUS TACROLIMUS 

分 类 号：R96[医药卫生—药理学]