Where does Lolitrem B bind to the human BK channel?

In collaboration with Dr Julie Dalziel, Biomembrane Laboratory

The large conductance calcium-activated potassium (BK) channel is both physiologically and medically important, having roles in bladder control, regulation of blood pressure, and motor function, and is therefore a potential target for new pharmaceuticals. Lolitrem B is an indole diterpene thought to be the main compound responsible for “ryegrass staggers”, a condition in which animals grazing on endophyte-infected pastures develop ataxia, tremors, and hypersensitivity to external stimuli. Indirect evidence suggests that Lolitrem B binds to the cytosolic domain of the BK channel. The aim of this project is to establish how the toxin inhibits the channel using a combination of biophysical and electrophysiological techniques.