RT Journal Article
SR Electronic
T1 Cannabidiol activates neuronal Kv7 channels
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.20.457154
DO 10.1101/2021.08.20.457154
A1 Zachary Niday
A1 Laurel Heckman
A1 Sooyeon Jo
A1 Han-Xiong Bear Zhang
A1 Akie Fujita
A1 Jaehoon Shim
A1 Roshan Pandey
A1 Hoor Al Jandal
A1 Selwyn Jayakar
A1 Jennifer A. Smith
A1 Clifford J. Woolf
A1 Bruce P. Bean
YR 2021
UL http://biorxiv.org/content/early/2021/08/21/2021.08.20.457154.abstract
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.