Cannabidiol activates neuronal Kv7 channels.

Zhang, Han-Xiong Bear; Heckman, Laurel; Niday, Zachary; Jo, Sooyeon; Fujita, Akie; Shim, Jaehoon; Pandey, Roshan; Al Jandal, Hoor et al. · Elife · 2022

basic_science · Level V

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Abstract

Cannabidiol (CBD), a chemical found in the <i>Cannabis sativa</i> plant, is a clinically effective antiepileptic drug whose mechanism of action is unknown. Using a fluorescence-based thallium flux assay, we performed a large-scale screen and found enhancement of flux through heterologously expressed human Kv7.2/7.3 channels by CBD. Patch-clamp recordings showed that CBD acts at submicromolar concentrations to shift the voltage dependence of Kv7.2/7.3 channels in the hyperpolarizing direction, producing a dramatic enhancement of current at voltages near -50 mV. CBD enhanced native M-current in mouse superior cervical ganglion starting at concentrations of 30 nM and also enhanced M-current in rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD may contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.

Medical subject headings