Actions of bis(7)-tacrine and tacrine on transient potassium current in rat DRG neurons and potassium current mediated by KV4.2 expressed in Xenopus oocyte

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 KV4.2 encoded potassium currents expressed in Xenopus oocytes and the transient A-type potassium current (IK(A)) on rat DRG neurons. Bis(7)-tacrine suppressed recombinant Kv4.2 potassium channels in a concentration-dependent manner, with IC50 value of 0.53 ± 0.13 μM. Tacrine also inhibited Kv4.2 channels, but with a much lower potency (IC50 74 ± 15 μM).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.