Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.

ABSTRACT: Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels.

SUBMITTER: Liin SI 

PROVIDER: S-EPMC6080886 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature