[Inhibition of tacrine on delayed rectifier and transient outward potassium currents in cultured rat hippocampal neurons].
OBJECTIVE
To study the effects of tacrine on IK and IA potassium current in primary cultured rat hippocampal neurons.


METHODS
Whole cell patch clamp and primary rat hippocampal neuron cultures were used.


RESULTS
Tacrine was shown to reduce the amplitude of IK and IA, in concentration-dependent manners. The IC50s at +40 mV for reduction of IK and IA were 23 and 52.6 mumol.L-1, respectively. Tacrine (30 mumol.L-1) shifted the steady state activation of IK and IA to negative potentials by 12 and 15 mV, respectively. The V1/2 of activation curves for IK current before and after the application of tacrine were (6.7 +/- 1.4) mV and (-5.4 +/- 1.3) mV, respectively. The k of activation curves for IK current was 13.4 + 1.3 and 12.5 + 1.4 without and with tacrine, respectively. The V1/2 of activation curve for IA current were (-9.9 +/- 2.6) mV and (-24 +/- 5) mV in the absence and presence of tacrine, respectively, and the k value was not changed.


CONCLUSIONS
Tacrine inhibited IK and IA currents in rat hippocampal neurons and it is more potent for blocking IK.
Zhang
Wei
W
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Jin
Hong-wei
HW
Xu
Shao-feng
SF
Qu
Lin-tao
LT
Wang
Xiao-liang
XL
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013619:Tacrine