<b><i>Introduction:</i></b> Voltage-gated Kv7/M potassium channels play an essential role in the control of membrane potential and neuronal excitability. Fangchinoline, a bisbenzylisoquinoline alkaloid, displays extensive biological activities including antitumor, anti-inflammatory, and antihypertension effects. In this study, we investigated the effects of fangchinoline on Kv7/M channels. <b><i>Methods:</i></b> A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from mouse dorsal root ganglion (DRG) neurons. <b><i>Results:</i></b> Fangchinoline inhibited Kv7.2/Kv7.3 currents in a concentration-dependent manner, with an IC<sub>50</sub> of 9.5 ± 1.2 μM. Fangchinoline significantly inhibited Kv7.1, Kv7.2, Kv7.3, Kv7.4, and Kv7.3/Kv7.5 channels without selective effects. Furthermore, fangchinoline significantly slowed the activation of Kv7.1-Kv7.5 channels and inhibited native M-channel currents of DRG neurons. <b><i>Conclusion:</i></b> Taken together, our findings indicate that fangchinoline concentration-dependently inhibited Kv7/M channel currents.
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