Purpose/Aim: 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, we explore the possible effects of tacrine on Kv2.1 channels in heterologous expression systems and N2A cells.Materials and methods: The change of expression and currents of Kv2.1 after treatment with tacrine was detected by PCR and whole-cell recordings, respectively. WST-8 experiments were performed to reveal the effects of tacrine on cell proliferation.Results: Incubation with tacrine induced a significant reduction of the mRNA level of Kv2.1 channels in HEK293 cells. The decline of corresponding currents carried by Kv2.1 was also observed. 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.Conclusion: 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.
Keywords: Kv2.1 channels; Tacrine; cell proliferation; expression; neuroprotection.