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Cannabidiol interactions with voltage-gated sodium channels

DOI: 10.7554/eLife.58593 DOI Help

Authors: Lily Goodyer Sait (Birkbeck College, University of London) , Altin Sula (Birkbeck College, University of London) , Mohammad-reza Ghovanloo (Simon Fraser University) , David Hollingworth (Birkbeck College, University of London) , Peter C. Ruben (Simon Fraser University) , Bonnie Wallace (Birkbeck College, University of London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 9

State: Published (Approved)
Published: October 2020

Open Access Open Access

Abstract: Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels.

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Other Facilities: P13 at DESY

Documents:
elife-58593-v2.pdf

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