Cannabidiol activates neuronal Kv7 channels
Han-Xiong Bear Zhang, Laurel M. Heckman, Zachary Niday, Sooyeon Jo, Akie Fujita, Jaehoon Shim, Roshan Pandey, Hoor Al Jandal, Selwyn S. Jayakar, Lee Barrett, Jennifer A. Smith, Clifford J. Woolf, Bruce P. Bean
Abstract
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.