PT  - JOURNAL ARTICLE
AU  - Zachary Niday
AU  - Laurel Heckman
AU  - Sooyeon Jo
AU  - Han-Xiong Bear Zhang
AU  - Akie Fujita
AU  - Jaehoon Shim
AU  - Roshan Pandey
AU  - Hoor Al Jandal
AU  - Selwyn Jayakar
AU  - Jennifer A. Smith
AU  - Clifford J. Woolf
AU  - Bruce P. Bean
TI  - Cannabidiol activates neuronal Kv7 channels
AID  - 10.1101/2021.08.20.457154
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.08.20.457154
4099  - http://biorxiv.org/content/early/2021/08/21/2021.08.20.457154.short
4100  - http://biorxiv.org/content/early/2021/08/21/2021.08.20.457154.full
AB  - Cannabidiol (CBD), a chemical found in the Cannabis sativa 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. Using patch clamp recordings, we found that CBD at low concentrations activates Kv7.2/7.3 channels at subthreshold voltages, with 100 nM CBD producing a doubling of current at -50 mV. CBD shifted the voltage-dependence of channels in the hyperpolarizing direction, producing a shift in the midpoint of activation by ∼-14 mV at 300 nM. CBD also effectively enhanced native M-current in both mouse superior cervical ganglion neurons and rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD seems likely to contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.Competing Interest StatementThe authors have declared no competing interest.