Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels.
Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] acts as an AChE inhibitor and also exerts modulatory effects on many ligand-gated ion channels and voltage-gated Ca(2+) and K(+) channels. It has been reported previously that tacrine and some other AChE inhibitors suppressed I(K(A)) in central and peripheral neurons. The present study aimed to explore whether bis(7)-tacrine could modulate the function of native delayed rectifier potassium channels in DRG neurons and K(V)1.2 encoded potassium channels expressed in oocytes. We found that both delayed rectifier potassium currents (I(K(DR))) in rat DRG neurons and the currents recorded from oocytes expressing K(V)1.2 (I(K(K(V)1.2))) were suppressed by bis(7)-tacrine, the potency of which was two orders greater than that of tacrine. The IC(50) values for bis(7)-tacrine and tacrine inhibition of I(K(KD)) in DRG neurons were 0.72+/-0.05 and 58.3+/-3.7 microM, respectively; while the two agents inhibited I(K(K(V)1.2)) in oocytes with an IC(50) of 0.24+/-0.06 and 102.1+/-21.5 microM, respectively. The possible mechanism for bis(7)-tacrine inhibition of I(K(A)) and I(K(K(V)1.2)) was identified as the suppression of their activation, inactivation.
Nie
Hui
H
Department of Neurobiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Yu
Wen-Jing
WJ
Li
Xiang-Yuan
XY
Yuan
Chun-Hua
CH
Pang
Yuan-Ping
YP
Li
Chao-Ying
CY
Han
Yi-Fan
YF
Li
Zhi-Wang
ZW
D000818:Animals; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D018014:Gene Transfer Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D051663:Kv1.2 Potassium Channel / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014981:Xenopus
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D051668:Delayed Rectifier Potassium Channels; D051663:Kv1.2 Potassium Channel; D026902:Potassium Channel Blockers; D013619:Tacrine