Authors
Ganesh, S., Canty, T. M., Sabatini, B. L.
Abstract
Fast-spiking parvalbumin-positive (PV) neurons provide precisely timed, context-dependent inhibition within cortical circuits. PV neuron firing properties are specialized among cortical neurons, suggesting that they express a unique complement of ion channels. Here, we identify the PV-specific silent voltage-gated potassium (Kv) channel subunit Kv6.4 (encoded by Kcng4) as a modulator of both intrinsic and synaptic properties. Kv6.4 does not form functional channels on its own but assembles with Kv2 subunits to create heterotetrameric channel complexes. Kcng4 expression is enriched within a distinct Pvalb-expressing subclass in primary somatosensory (S1) and motor (M1) cortex and emerges during postnatal development. Kv6.4 depolarizes the interspike and threshold potentials, broadens action potentials (APs), increases AP height, and decelerates the AP upstroke. These changes in AP waveform enhance GABA release probability and paired-pulse depression at synapses made by PV onto pyramidal (PYR) neurons. The effects of Kv6.4 loss are amplified during high-frequency firing, within the physiological range of fast-spiking PV neurons, likely due to altered repolarization dynamics that accumulate across successive APs. These findings are thus consistent with the function of Kv6.4 in modifying Kv2-mediated delayed rectifier currents. Hence, Kv6.4 tunes the temporal precision of PV inhibitory output, a feature that may be critical for stable excitation-inhibition ratios and adaptive circuit function underlying learning and behavior.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Nov 2025.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 46
- Comments 0