Understanding the binding of drugs to voltage gated sodium channel fenestrations

Drug binding at the fenestration site is known to block Navs and stabilise the inactivated state of the channel, but the specific nature of the site, why the inactivated state is stabilised and whether subtype selective binding can be achieved are not well understood. This project will aim to1. Better characterise the nature of the fenestration binding site and the central pore cavity2. Elucidate how binding at the fenestration site alters the structure and functional state of the channel3. Explain how subtype selectivity can arise at the fenestration binding site