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 M.; Richardson, Amy; Anderson, Michelle; Robinson, Susan W.; Marra, Vincenzo; Ciampani, Victoria; Walter, Sophie M.; Kopp-Scheinpflug, Conny; Steinert, Joern R. und Forsythe, Ian D. (4. April 2020): Kv3.1 and Kv3.3 subunits differentially contribute to Kv3 channels and action potential repolarization in principal neurons of the auditory brainstem. In: Journal of Physiology, Bd. 598, Nr. 11: S. 2199-2222

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.

• Dokumententyp: Zeitschriftenartikel
• Keywords: auditory system; potassium channel; voltage clamp
• Fakultät: Biologie > Department Biologie II > Neurobiologie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie
• Bemerkung: PMID: 32246836
• Sprache: Englisch