Open AccessElectrophysiological actions of cyclosporin A and tacrolimus on rat hippocampal CA1 pyramidal neurons 1
Author(s) -
YU Yong,
CHEN Xueqin,
CUI Yaoyuan,
HU Guoyuan
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00730.x
Subject(s) - hippocampal formation , electrophysiology , tacrolimus , neuroscience , hippocampus , medicine , pyramidal cell , pharmacology , chemistry , biology , transplantation
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 ( I K ) in a concentration‐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 K by CsA (100 μmol/L) persisted under the low Ca 2+ conditions that blocked the basal activity of calcineurin. Conclusion : CsA exerted calcineurin‐independent inhibition on the I K 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 I K .