Cannabidiol interactions with voltage-gated sodium channels
| Autor: | Peter C. Ruben, Bonnie A. Wallace, Altin Sula, Lily Goodyer Sait, David Hollingworth, Mohammad-Reza Ghovanloo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
crystal structure
structure-function relationships QH301-705.5 Protein Conformation Sodium Science Structural Biology and Molecular Biophysics TRPV2 High resolution chemistry.chemical_element Voltage-Gated Sodium Channels Crystallography X-Ray digestive system General Biochemistry Genetics and Molecular Biology 03 medical and health sciences cannabidiol 0302 clinical medicine None medicine Biology (General) Tetrahydrocannabinol 030304 developmental biology 0303 health sciences Binding Sites General Immunology and Microbiology Chemistry General Neuroscience Sodium channel Molecular biophysics drug interations General Medicine electrophysiology digestive system diseases 3. Good health Electrophysiology surgical procedures operative Structural biology Target site Molecular mechanism Biophysics Medicine Cannabidiol Sequence Alignment 030217 neurology & neurosurgery voltage -gated sodium channel medicine.drug Research Article |
| Zdroj: | eLife eLife, Vol 9 (2020) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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