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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

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posted on 2020-04-16, 12:26 authored by Nasreen Choudhury, Deborah Linley, Michelle Anderson, Susan Robinson, Vincenzo Marra, Victoria Ciampani, Sophie Walter, Conny Kopp-Scheinpflug, Joern Steinert, Ian Forsythe, Amy Richardson
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. Assembly of Kv3 channels was constrained to either Kv3.1 or Kv3.3 in principal neurons of the Medial Nucleus of the Trapezoid Body (MNTB) and Lateral Superior Olive (LSO); while tetraethylammonium (TEA, 1 mM) was employed to block Kv3‐mediated outward potassium currents in voltage‐ and current‐clamp experiments. MNTB neuron APs (halfwidth 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 halfwidths were also fast, but absolutely required Kv3.3 subunits for fast repolarization (halfwidths: 0.25 ± 0.08 ms, n = 19 WT, 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 the respective 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 brainstem nuclei involved in sound localization.


This work was funded by a project grant from the BBSRC (NC, MA, JRS, IDF), a BBSRC PhD Case Studentship (AR/IDF); MRC intramural funding (SWR), and a PhD Scholarship (DL/IDF) from Action on Hearing Loss (AoHL). SMW received an Erasmus+ traineeship from Freie University, Berlin Germany.



The Journal of Physiology, 2020

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