Inhibition by bis(7)-tacrine of native delayed rectifier and KV1.2 encoded potassium channels

Abstract 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 μM, 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 μM, 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.