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Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem

Choudhury, Nasreen; Linley, Deborah; Richardson, Amy; Anderson, Michelle; Robinson, Susan W.; Marra, Vincenzo; Ciampani, Victoria; Walter, Sophie M.; Kopp‐Scheinpflug, Conny; Steinert, Joern R.; Forsythe, Ian D.

Authors

Nasreen Choudhury

Deborah Linley

Amy Richardson

Michelle Anderson

Susan W. Robinson

Vincenzo Marra

Victoria Ciampani

Sophie M. Walter

Conny Kopp‐Scheinpflug

Ian D. Forsythe



Abstract

Kv3 voltage-gated potassium channels mediate action potential (AP) repolarization. The relative importance of Kv3.1 and Kv3.3 subunits for assembly of functional channels in neurons of the auditory brainstem was examined from the physiological perspective that speed and precision of AP firing are crucial for sound source localization. High levels of Kv3.1 and Kv3.3 mRNA and protein were measured, with no evidence of compensation by Kv3.2 or Kv3.4 in the respective knockout (KO) mouse. Using the KOs, composition of Kv3 channels was constrained to either Kv3.1 or Kv3.3 subunits in principal neurons of the medial nucleus of the trapezoid body (MNTB) and lateral superior olive (LSO); while TEA (1 mm) was employed to block Kv3-mediated outward potassium currents in voltage- and current clamp experiments. MNTB neuron APs (half-width 0.31 ± 0.08 ms, n = 25) were fast, reliable, and showed no distinction between channels assembled from Kv3.1 or Kv3.3 subunits (in the respective KO). LSO AP half-widths were also fast, but absolutely required Kv3.3 subunits for fast repolarization (half-widths: 0.25 ± 0.08 ms, n = 19 wild-type, 0.60 ± 0.17 ms, n = 21 Kv3.3KO, p = 0.0001). The longer AP duration increased LSO calcium influx and AP failure rates, and increased AP latency and jitter during high frequency repetitive firing. Both Kv3.1 and Kv3.3 subunits contribute to Kv3 channels in the MNTB (and compensate for each other in each KO); in contrast, LSO neurons require Kv3.3 subunits for fast repolarization and to sustain AP firing during high frequency stimulation. In conclusion, Kv3 channels exhibit both redundancy and Kv3.3 dominance between the brainstem nuclei involved in sound localization.

Journal Article Type Article
Acceptance Date Mar 25, 2020
Online Publication Date May 16, 2020
Publication Date Jun 1, 2020
Deposit Date Oct 28, 2022
Publicly Available Date Nov 1, 2022
Journal Journal of Physiology
Print ISSN 0022-3751
Electronic ISSN 1469-7793
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 598
Issue 11
Pages 2199-2222
DOI https://doi.org/10.1113/jp279668
Keywords Physiology
Public URL https://nottingham-repository.worktribe.com/output/12902138
Publisher URL https://physoc.onlinelibrary.wiley.com/doi/10.1113/JP279668

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