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


RESULTS
CsA (100 micromol/L) and FK506 (50 micromol/L) did not significantly alter the passive electrical properties of hippocampal CA1 pyramidal neurons, but slowed down the repolarizing phase of the action potential. CsA (10-100 micromol/L) selectively inhibited the delayed rectifier K+ current (IK) in a concentration-dependent manner. CsA did not affect the kinetic properties of IK. Intracellular dialysis of CsA (100 micromol/L) had no effect on IK. The inhibition of IK by CsA (100 micromol/L) persisted under the low Ca2+ conditions that blocked the basal activity of calcineurin.


CONCLUSIONS
CsA exerted calcineurin-independent inhibition on the IK 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 IK.
Yu
Yong
Y
Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Chen
Xue-qin
XQ
Cui
Yao-yuan
YY
Hu
Guo-yuan
GY
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus