论文部分内容阅读
Aim:The aim of the present study was to investigate the electrophysiologicalactions of cyclosporin A (CsA) and tacrolimus (FK506) on neurons in the brain,and to elucidate the relevant mechanisms.Methods:Whole-cell current-clamprecording 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 μmol/L) and FK506 (50 μmol/L) did notsignificantly alter the passive electrical properties of hippocampal CA 1 pyramidalneurons,but slowed down the repolarizing phase of the action potential.CsA(10-100 μmol/L) selectively inhibited the delayed rectifier K~+ current (I_K) in aconcentration-dependent manner.CsA did not affect the kinetic properties of I_K.Intracellular dialysis of CsA (100 μmol/L) had no effect on I_K.The inhibition of I_Kby CsA (100 μmol/L) persisted under the low Ca~(2+) conditions that blocked thebasal activity of calcineurin.Conclusion:CsA exerted calcineurin-independentinhibition on the I_K in rat hippocampal pyramidal neurons.Taken together withour previous finding with FK506,it is conceivable that the spike broadening causedby the immunosuppressant drugs is due to direct inhibition on the I_K.
Aim: The aim of the present study was to investigate the electrophysiologicalactions 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 μmol / L) and FK506 (50 μmol / L) did not significantly differ from the passive electrical properties of hippocampal CA 1 pyramidalneurons, but slowed down the repolarizing phase of the action potential. CsA (10-100 μmol / L) selectively inhibited the delayed rectifier K ~ + current (I_K) in aconcentration-dependent manner.CsA did not affect the kinetic properties of I_K.Intracellular dialysis of CsA (100 μmol / L) had no effect on I_K.The inhibition of I_Kby CsA (100 μmol / L) persisted under the low Ca ~ (2) conditions that blocked the basal activity of calcineurin.Conclusion : CsA exerted calcin eurin-independent inhibition of the I_K in rat hippocampal pyramidal neurons. Together with your previous findings with FK506, it is conceivable that the spike broadening caused by the immunosuppressant drugs is due to direct inhibition on the I_K.