Cannabidiol activates neuronal Kv7 channels
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. Patch-clamp recordings showed that CBD acts at submicromolar concentrations to shift the voltage dependence of Kv7.2/7.3 channels in the hyperpolarizing direction, producing a dramatic enhancement of current at voltages near –50 mV. CBD enhanced native M-current in mouse superior cervical ganglion starting at concentrations of 30 nM and also enhanced M-current in rat hippocampal neurons. The potent enhancement of Kv2/7.3 channels by CBD may contribute to its effectiveness as an antiepileptic drug by reducing neuronal hyperexcitability.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 18, 2022
- Source ID
- 10.7554/elife.73246
Entities
People
- Akie Fujita
- Bruce P. Bean
- Clifford J. Woolf
- Han-xiong Bear Zhang
- Hoor Al Jandal
- Jaehoon Shim
- Jennifer E Smith
- Laurel Heckman
- Lee B Barrett
- Roshan Pandey
- Selwyn Jayakar
- Sooyeon Jo
- Zachary Niday
Organizations
- Boston Children's Hospital
- Defense Advanced Research Projects Agency
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Harvard Medical School
- National Institute of Neurological Disorders and Stroke