Function and pharmacology of human Na+-activated K+ channels

Lead Research Organisation: University of Leeds
Department Name: Institute of Membrane & Systems Biology

Abstract

Inherited and spontaneous gain-of-function mutations in the human KCNT1 gene, which encodes the SLACK Na+-activated K+ channel, have recently been linked to severe and drug-resistant epilepsies. Children suffering from these disorders have poor quality of life and many do not survive to adulthood. Inhibiting this channel with a potent and selective small molecule therapeutic is therefore a prioritised strategy for the treatment of these epilepsies. The SLACK channel is a poorly studied and understood potassium channel, with the Leeds group one of only a handful of laboratories with experience in studying its function, pharmacology, and effects of mutations. Underpinning fundamental research is required to understand (a) how exactly the epilepsy-related mutations affect both the structure and function of the channel, and (b) the mechanism by which known inhibitors and activators exert their effects.

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
1943414 Studentship BB/M011151/1 30/09/2017 29/09/2021 Bethan Cole
 
Title Concatemeric WT/mutant KCNT1 plasmid DNA 
Description Used molecular biology techniques to produce concatemeric channels formed of wt and mutant subunits. This enables us to better study the effects of heterozygous epilepsy-causing KCNT1 mutations on channel function; since most research to date has looked at homomeric channels. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2019 
Provided To Others? No  
Impact N/A 
 
Description Autifony Therapeutics 
Organisation Autifony Therapeutics
Country United Kingdom 
Sector Private 
PI Contribution I will be visiting Autifony for three months to carry out experiments in Sept 2020.
Collaborator Contribution Autifony have provided us with a stable KNa1.1 cell line to use for experiments.
Impact N/A
Start Year 2017