Hu_2019_Int.J.Neurosci__1

Besides as a cholinesterase (ChE) inhibitor, tacrine is able to act on multiple targets such as nicotinic receptors (nAChRs) and voltage-gated K(+) (Kv) channels. Kv2.1, a Kv channel subunit underlying delayed rectifier currents with slow kinetics of inactivation, is highly expressed in the mammalian brain, especially in the hippocampus. Nevertheless, limited data are available concerning the relationship between tacrine and Kv2.1 channels. In the present study, incubation with tacrine induced a significant reduction of the mRNA level of Kv2.1 channels heterologously expressed in HEK293 cells. The decline of corresponding currents carried by Kv2.1 was also detected by whole-cell recording. Moreover, the proliferation rates of HEK293 cells with Kv2.1 channel were substantially enhanced after treatment with this chemical for 24 h. Similar results were also detected after exposure to tacrine in N2A cells with native expression of Kv2.1 channels. These lines of evidence indicate that application of tacrine downregulates the expression of Kv2.1 channels and increase cell proliferation. The effect of tacrine on Kv2.1 channels may provide an alternative explanation for its neuroprotective action.