Voltage-dependent structural changes in voltage-gated sodium channels (2016-2018)

Voltage-gated sodium (Nav) channels initiate action potentials in excitable cells. They open in response to membrane depolarisation then rapidly inactivate. Eukaryotic Nav channels contain four unique voltage-sensor domains (VSDs) that control how the channel responds to membrane potential changes. Recently reported crystal structures of bacterial Nav channels have greatly advanced the field, but these channels contain four identical VSDs and have different inactivation properties. Thus, much remains to be learnt about the conformational plasticity of eukaryotic Nav channel VSDs. We will use animal toxins to capture eukaryotic VSDs in defined states of the gating cycle for detailed structural analysis using NMR and X-ray crystallography.