VU0810464, a non-urea G protein-gated inwardly rectifying K⁺ (K_ir 3/GIRK) channel activator, exhibits enhanced selectivity for neuronal K_ir 3 channels and reduces stress-induced hyperthermia in mice.

ABSTRACT:

Background and purpose

G protein-gated inwardly rectifying K⁺ (K_ir 3) channels moderate the activity of excitable cells and have been implicated in neurological disorders and cardiac arrhythmias. Most neuronal K_ir 3 channels consist of K_ir 3.1 and K_ir 3.2 subtypes, while cardiac K_ir 3 channels consist of K_ir 3.1 and K_ir 3.4 subtypes. Previously, we identified a family of urea-containing K_ir 3 channel activators, but these molecules exhibit suboptimal pharmacokinetic properties and modest selectivity for K_ir 3.1/3.2 relative to K_ir 3.1/3.4 channels. Here, we characterize a non-urea activator, VU0810464, which displays nanomolar potency as a K_ir 3.1/3.2

SUBMITTER: Vo BN 

PROVIDER: S-EPMC6555862 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature