Cannabidiol activates neuronal Kv7 channels

Han-Xiong Bear Zhang; Laurel M. Heckman; Zachary Niday; Sooyeon Jo; Akie Fujita; Jaehoon Shim; Roshan Pandey; Hoor Al Jandal; Selwyn S. Jayakar; Lee B Barrett; Jennifer A. Smith; Clifford J. Woolf; Bruce P. Bean

doi:10.7554/elife.73246

NeuroscienceeLifeFeb 10, 2022

Peer-reviewed journal article

Cannabidiol activates neuronal Kv7 channels

Han-Xiong Bear Zhang iD, Laurel M. Heckman iD, Zachary Niday, Sooyeon Jo iD, Akie Fujita iD, Jaehoon Shim iD, Roshan Pandey, Hoor Al Jandal iD, Selwyn S. Jayakar iD, Lee B Barrett, Jennifer A. Smith iD, Clifford J. Woolf iD, Bruce P. Bean iD

Abstract

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.

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