Neurotransmitter redesigned to activate potassium channels
Scientists from UC Irvine used computational approach and minor experimental screening. They compared neurotransmitters – such as GABA and glycine – in terms of binding and effects on potassium channels. Although they found that GABA activates KCNQ channels (type 2/3, 3, and 5), similar glycine was not activating KCNQ. However, introduction of fluorophenyl groups to the glycine molecule changed its activity.
Three derivatIves of glycine – 2FPG, 4FPG, 3FMSG – shifted membrane potential more than retigabine, synthetic anticonvulsant. Combined compounds synergistically activated KCNQ type 2/3.
The can support understanding and treatment of rare genetic disorders caused by mutations in KCNQ genes. Moreover, authors suggest that created compounds can aid pharmacological approach to convulsions.
Publication: Manville, R. W., & Abbott, G. W. (2019). In silico re-engineering of a neurotransmitter to activate KCNQ potassium channels in an isoform-specific manner. Communications Biology, 2(1). doi:10.1038/s42003-019-0648-3
Photo: Judith Stoffer