K_2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site.

ABSTRACT: Polymodal thermo- and mechanosensitive two-pore domain potassium (K_2P) channels of the TREK subfamily generate 'leak' currents that regulate neuronal excitability, respond to lipids, temperature and mechanical stretch, and influence pain, temperature perception and anaesthetic responses. These dimeric voltage-gated ion channel (VGIC) superfamily members have a unique topology comprising two pore-forming regions per subunit. In contrast to other potassium channels, K_2P channels use a selectivity filter 'C-type' gate as the principal gating site. Despite recent advances, poor pharmacological profiles of K_2P channels limit mechanistic and biological studies. Here we describe a class of small-molecule TREK activators that directly stimulate the C-type gate by a

SUBMITTER: Lolicato M 

PROVIDER: S-EPMC5778891 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature