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Changes in Kv3 currents and action potential (AP) firing were analysed from wild\u2010type, Kv3.1 and Kv3.3 knockout (KO) mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both Kv3.1 and Kv3.3 immunostaining was present and western blots confirmed loss of subunit protein in the respective KO.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Medial nucleus of the trapezoid body (MNTB) AP repolarization utilized Kv3.1 and\/or Kv3.3; while in the lateral superior olive (LSO) Kv3.3 was essential.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Voltage\u2010gated calcium currents were unchanged between the genotypes. But APs evoked higher [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> in LSO than MNTB neurons; and were highest in the Kv3.3KO, consistent with longer AP durations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>High frequency stimulation increased AP failure rates and AP latency in LSO neurons from the Kv3.3KO, underlining the physiological consequences for binaural integration.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>LSO neurons require Kv3.3 for functional Kv3 channels, while MNTB neurons can utilize either Kv3.1 or Kv3.3 subunits.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Kv3 voltage\u2010gated 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\u00a0m<jats:sc>m<\/jats:sc>) was employed to block Kv3\u2010mediated outward potassium currents in voltage\u2010 and current clamp experiments. MNTB neuron APs (half\u2010width 0.31\u00a0\u00b1\u00a00.08\u00a0ms, <jats:italic>n<\/jats:italic>\u00a0=\u00a025) were fast, reliable, and showed no distinction between channels assembled from Kv3.1 or Kv3.3 subunits (in the respective KO). LSO AP half\u2010widths were also fast, but absolutely required Kv3.3 subunits for fast repolarization (half\u2010widths: 0.25\u00a0\u00b1\u00a00.08\u00a0ms, <jats:italic>n<\/jats:italic>\u00a0=\u00a019 wild\u2010type, 0.60\u00a0\u00b1\u00a00.17\u00a0ms, <jats:italic>n<\/jats:italic>\u00a0=\u00a021 Kv3.3KO, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0001). 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.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279668","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T19:24:57Z","timestamp":1586028297000},"page":"2199-2222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem"],"prefix":"10.1113","volume":"598","author":[{"given":"Nasreen","family":"Choudhury","sequence":"first","affiliation":[{"name":"Auditory Neurophysiology Laboratory, Department of Neuroscience Psychology &amp; Behaviour College of Life Sciences University of Leicester  Leicester LE1 7RH 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