Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

Citation

Richardson A, Ciampani V, Stancu M, Bondarenko K, Newton S, Steinert JR, Pilati N, Graham BP, Kopp-Scheinpflug C & Forsythe ID (2022) Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse. eLife, 11 (1), Art. No.: e75219. https://doi.org/10.7554/elife.75219

Abstract
Kv3 potassium currents mediate rapid repolarisation of action potentials (APs), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal in the mouse. Deletion of Kv3.3 (but not Kv3.1) reduced presynaptic Kv3 channel immunolabelling, increased presynaptic AP duration and facilitated excitatory transmitter release; which in turn enhanced short-term depression during high-frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 mediates fast repolarisation for short precise APs, conserving transmission during sustained high-frequency activity at this glutamatergic excitatory synapse.

Keywords
General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience

Journal
eLife: Volume 11, Issue 1

People

Professor Bruce Graham

Emeritus Professor, Computing Science