title: Actions of bis(7)-tacrine and tacrine on transient potassium current in rat DRG neurons and potassium current mediated by K(V)4.2 expressed in Xenopus oocyte.
abstract: Bis(7)-tacrine [bis(7)-tetrahydroaminacrine] is a dimeric AChE inhibitor derived from tacrine with a potential to treat Alzheimer's disease. Actions of bis(7)-tacrine on ligand-gated ion channels and voltage-gated cation channels have been identified on neurons of both central and peripheral nervous systems. In the present study, the effect of bis(7)-tacrine was investigated on the K(V)4.2 encoded potassium currents expressed in Xenopus oocytes and the transient A-type potassium current (I(K(A))) on rat DRG neurons. Bis(7)-tacrine suppressed recombinant Kv4.2 potassium channels in a concentration-dependent manner, with IC(50) value of 0.53+/-0.13 muM. Tacrine also inhibited Kv4.2 channels, but with a much lower potency (IC(50) 74+/-15 muM).The possible mechanisms underlying the inhibition on potassium currents by bis(7)-tacrine/tacrine could be that inactivation of the transient potassium currents was accelerated and recovery of the native or Kv4.2 expressed potassium currents was suppressed by bis(7)-tacrine/tacrine.
authors.affiliation: Institute for Electronics and Informatics, South-Central University for Nationalities, Wuhan 430074, PR China.
authors.forename: Xiang-Yuan
authors.initials: XY
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Jia-Pei
authors.initials: JP
authors.lastname: Dai
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Zhi-Wang
authors.initials: ZW
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D018014:Gene Transfer Techniques; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013619:Tacrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D002800:Cholinesterase Inhibitors; D015221:Potassium Channels; D011994:Recombinant Proteins; D051672:Shal Potassium Channels; D013619:Tacrine; D011188:Potassium