Bethan Cole

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

About me

I completed my degree in Pharmacology (BSc hons) at the University of Bristol in 2017, before moving to the University of Leeds for my PhD. I am interested in using electrophysiological techniques to study the role of potassium channels in normal human physiology, and channelopathies associated with dysfunction of these ion channels.

My project

Missense, gain-of-function mutations of KCNT1, the gene encoding subunits of Na+-activated K+ channel Slack, are associated with early-onset epileptic encephalopathies. Children with these disorders have a poor quality of life, suffer from accompanying intellectual disabilities, and often do not survive until adulthood. The diseases are pharmacoresistant; antiarrhythmic drugs have shown some efficacy, but are accompanied by adverse cardiac effects due to their poor selectivity for Slack channels. Therefore, development of a potent and selective inhibitor without accompanying adverse effects is crucial.
There is significant variation in the phenotypes arising from channel mutation, and mechanisms of channel gating are unclear. My project is aiming to further our understanding of how exactly the epilepsy-causing mutations are affecting structure and function of the channel, and the mechanisms by which known inhibitors are exerting their effects. I will be employing a range of electrophysiological techniques to study the function and pharmacology of wildtype and mutant Slack channels.