UCL Division of Biosciences


NPP Seminar - Professor Ian Forsythe, University of Leicester

02 November 2022, 1:00 pm–2:00 pm

Ian D Forsythe University of Leicester

Title: “A special role for Kv3.3 potassium channel subunits in presynaptic action potential repolarization.”

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Charlette Bent-Gayle


G46 H O Schild Pharmacology LT,
Medical Sciences and Anatomy
Gower Street
United Kingdom

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.

About the Speaker

Professor Ian Forsythe

Emeritus Professor of Neurophysiology at University of Leicester

I lead a group interested in mechnisms of synaptic transmission and neuronal integration, with a particular focus in the neurophysiology of the auditory pathway. Our work includes mechanisms of transmisison at the calyx of Held, studies of voltage-gated potassium channels and the modulation of intrinsic neuronal excitability by nitric oxide signalling. Currently we are exploring the mechanisms by which Kv3 potassium channel subunits differentially contribute to action potential waveforms in the soma and presynaptic terminal. We are also studying the influence that ATP metabolism (and the substrates used to generate ATP) has on neuronal excitability and synaptic transmission.

More about Professor Ian Forsythe