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.
People |
ORCID iD |
Jonathan Lippiat (Primary Supervisor) |
Publications
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 |
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 |