NPP Seminar - Professor Ian Forsythe, University of Leicester

Academic Hosts: Annette Dolphin

Abstract: Potassium channels are the foundation upon which all other forms of neuronal excitability are built. They are diverse, with more than 80 genes specifying potassium channel subunits in around 12 different families. The four voltage-gated potassium channel families (kcna-kcnd) are particularly important in setting action potential firing threshold, firing rate and action potential waveform.  The kcnc/Kv3 voltage-gated potassium channel family has four genes specifying 4 subunits (Kv3.1 – Kv3.4). We have been investigating the physiological role of these subunits, focusing on Kv3.1 and Kv3.3 in setting the ‘biophysical speed-limit’ for action potential repolarization.  We have studied their physiology in the context of brainstem auditory processing and the integration of sensory information. This system includes the calyx of Held giant synapse from which we can gain insights into the presynaptic role of Kv3 channels. Our results show that Kv3.3 subunits are necessary to maximise action potential repolarization at the fastest nerve terminals. However they are not expressed at all terminals, so Kv3.3 is not ‘essential’, and we postulate that they form part of the machinery necessary to achieve efficient nanodomain signalling at the fastest synaptic terminals. We are also investigating the mechanism by which point mutations of Kv3.3 cause Spinocerebellar Ataxia type 13 (SCA13) which underlies auditory processing disorders, other sensory disorders, epilepsy and neurodegeneration in the cerebellum. We conclude that Kv3 channels containing Kv3.3 subunits are necessary for high frequency transmission at fast synapses.