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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.
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Highlights • The K2P TRAAK has physically distinct leak and mechanically activated open states • FHEIG syndrome-causing mutations promote mechanically activated openings • A pan-K2P activating mutation in the channel cavity promotes leak openings • Leak openings occur with TM4 down and mechanically activated openings with TM4 up Summary TRAAK is a mechanosensitive two-pore domain K+ (K2P) channel localized to nodes of Ranvier in myelinated neurons.
Abstract SARS-CoV-2 ORF3a is a putative viral ion channel implicated in autophagy inhibition, inflammasome activation and apoptosis. 3a protein and anti-3a antibodies are found in infected patient tissues and plasma. Deletion of 3a in SARS-CoV-1 reduces viral titer and morbidity in mice, suggesting it could be an effective target for vaccines or therapeutics. Here, we present structures of SARS-CoV-2 3a determined by cryo-EM to 2.1-Å resolution.
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