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: Xiang-Yuan Li, Jian Zhang, Jia-Pei Dai, Xiang-Ming Liu, Zhi-Wang Li
• Journal: Brain research (Brain Res) Vol. 1318 Pg. 23-32 (Mar 08 2010) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 20043893 (Publication Type: Journal Article)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
• Cholinesterase Inhibitors
• Potassium Channels
• Recombinant Proteins
• Shal Potassium Channels
• Tacrine
• Potassium

Topics

• Animals
• Cells, Cultured
• Cholinesterase Inhibitors (administration & dosage, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Ganglia, Spinal (drug effects, physiology)
• Gene Transfer Techniques
• Inhibitory Concentration 50
• Membrane Potentials (drug effects)
• Neurons (drug effects, physiology)
• Oocytes
• Potassium (metabolism)
• Potassium Channels (metabolism)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (genetics, metabolism)
• Shal Potassium Channels (genetics, metabolism)
• Tacrine (administration & dosage, analogs & derivatives, chemistry, pharmacology)
• Xenopus laevis