Acta Pharmacologica Sinica 2007 December; 28 (12): 1891-1897; doi: 10.1111/j.1745-7254.2007.00730.x

 
Original Article
[ Full text ]
 
Electrophysiological actions of cyclosporin A and tacrolimus on rat hippocampal CA1 pyramidal neurons1
 

Yong YU2, Xue-qin CHEN3, Yao-yuan CUI2,4, Guo-yuan HU3,4

2Department of Neurosurgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; 3State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

 

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 pyramidal neurons of rats.

 

Results: CsA (100 µmol/L) and FK506 (50 µmol/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 µmol/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 µmol/L) had no effect on IK. The inhibition of IK by CsA (100 µmol/L) persisted under the low Ca2+ conditions that blocked the basal activity of calcineurin.


Conclusion:
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.

 

Keywords: action potential; calcineurin; cyclosporin A; delayed rectifier K+ channel; hippocampus; tacrolimus

 
1 Project partly supported by a grant from the National Natural Science Foundation of China (No 30472086).

4 Correspondence to Prof Yao-yuan CUI and Prof Guo-yuan HU.
Phn 86-21-6404-1990, ext 2011.
E-mail cyy@zshospital.com (Yao-yuan CUI)
Phn 86-21-5080-6778.
E-mail gyhu@mail.shcnc.ac.cn (Guo-yuan HU)
Received 2007-05-24     Accepted 2007-08-14

[ Full text ]
 

Copyright©APS 2009
Add: 294 Tai-Yuan Road, Shanghai 200031, China
Phn: 86-21-5492-2821  Fax: 86-21-5492-2823
E-mail: aps@mail.shcnc.ac.cn