Voltage-gated potassium (Kv) channels are a large family of ion channels that transport potassium ions across the plasma membrane in response to changes in membrane potential. Kv3.1, one of the four members comprising Kv3 subfamily, is the main channel for rapid membrane repolarisation upon large depolarisation in fast-spiking neurones, making it a therapeutics target for neurological disorders such as epilepsy, Fragile X Syndrome, and age-related hearing loss.
Here I present the insights on the molecular physiology of human Kv3.1 gained from a series of high-resolution structures. Our structures indicate that its tetramerisation domain plays important roles in intracellular trafficking and interactions with accessory proteins. Additionally, we explore the mechanism of energy transfer from the voltage-sensing domain (VSD) to the potassium-conducting pore domain (PD) with structure-guided mutation studies. These discoveries add to our knowledge of Kv channel molecular physiology and will aid structure-guided approaches to drug discovery.