Effect of two activators on the gating of a K_2P channel.

ABSTRACT: TWIK-related potassium channel 1 (TREK1), a two-pore-domain mammalian potassium (K⁺) channel, regulates the resting potential across cell membranes, presenting a promising therapeutic target for neuropathy treatment. The gating of this channel converges in the conformation of the narrowest part of the pore: the selectivity filter (SF). Various hypotheses explain TREK1 gating modulation, including the dynamics of loops connecting the SF with transmembrane helices and the stability of hydrogen bond (HB) networks adjacent to the SF. Recently, two small molecules (Q6F and Q5F) were reported as activators that affect TREK1 by increasing its open probability in single-channel current measurements. Here, using molecular dynamics simulations, we investigate the effect of these ligands o

SUBMITTER: Mendez-Otalvaro E 

PROVIDER: S-EPMC11480771 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature