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Updated: Jun 4, 2025

Exploring Arterial Smooth Muscle Kv7 Potassium Channel Function using Patch Clamp Electrophysiology and Pressure Myography
Published on: September 14, 2012
Cannabinoid inhibition of mechanosensitive K+ channels
Trevor Docter1, Ben Sorum1, Rahul Deshmane1
1Department of Molecular & Cell Biology, Department of Neuroscience, California Institute for Quantitative Biology (QB3), University of California Berkeley, Berkeley, California 94720, USA.
Abstract:
Cannabidiol (CBD) is a prominent non-psychoactive small molecule produced by cannabis plants used clinically as an antiepileptic. Here, we show CBD and other cannabinoids are potent inhibitors of mechanosensitive two-pore domain K+ (K2P) channels, including TRAAK and TREK-1 that contribute to spike propagation in myelinated axons. Five TRAAK mutations that cause epilepsy or the neurodevelopmental syndrome FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth) retain sensitivity to cannabinoid inhibition. A cryo-EM structure reveals CBD binds in the intracellular cavity of TREK-1 to sterically block ion conduction. These results show that cannabinoids and endogenous lipids compete for a common binding site to inhibit channel activity, identify mechanosensitive K2Ps as potential physiological targets of CBD, and suggest cannabinoids could counter gain-of-function in TRAAK channelopathies.
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