title: Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1.
abstract: A low voltage-activated potassium current, IKL, is found in auditory neuron types that have low excitability and precisely preserve the temporal pattern of activity present in their presynaptic inputs. The gene Kcna1 codes for Kv1.1 potassium channel subunits, which combine in expression systems to produce channel tetramers with properties similar to those of IKL, including sensitivity to dendrotoxin (DTX). Kv1.1 is strongly expressed in neurons with IKL, including auditory neurons of the medial nucleus of the trapezoid body (MNTB). We therefore decided to investigate how the absence of Kv1.1 affected channel properties and function in MNTB neurons from mice lacking Kcna1. We used the whole cell version of the patch clamp technique to record from MNTB neurons in brainstem slices from Kcna1-null (-/-) mice and their wild-type (+/+) and heterozygous (+/-) littermates. There was an IKL in voltage-clamped -/- MNTB neurons, but it was about half the amplitude of the IKL in +/+ neurons, with otherwise similar properties. Consistent with this, -/- MNTB neurons were more excitable than their +/+ counterparts; they fired more than twice as many action potentials (APs) during current steps, and the threshold current amplitude required to generate an AP was roughly halved. +/- MNTB neurons had excitability and IKL amplitudes identical to the +/+ neurons. The IKL remaining in -/- neurons was blocked by DTX, suggesting the underlying channels contained subunits Kv1.2 and/or Kv1.6 (also DTX-sensitive). DTX increased excitability further in the already hyperexcitable -/- MNTB neurons, suggesting that -/- IKL limited excitability despite its reduced amplitude in the absence of Kv1.1 subunits.
authors.affiliation: The Virginia Merrill Bloedel Hearing Research Center and the Department of Otolaryngology - Head and Neck Surgery, Box 357923, University of Washington School of Medicine, Seattle, WA 98195, USA. hbrew@u.washington.edu
authors.forename: Helen M
authors.initials: HM
authors.lastname: Brew
authors.forename: Janice L
authors.initials: JL
authors.lastname: Hallows
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Tempel
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D004247:DNA / Q000235:genetics; D004546:Elapid Venoms / Q000494:pharmacology; D004594:Electrophysiology; D005838:Genotype; D006309:Hearing / Q000502:physiology*; D007150:Immunohistochemistry; D051662:Kv1.1 Potassium Channel; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000235:genetics* / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D050765:Qa-SNARE Proteins
chemical_list: D004546:Elapid Venoms; C496947:Kcna1 protein, mouse; D008565:Membrane Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D050765:Qa-SNARE Proteins; D051662:Kv1.1 Potassium Channel; C020273:dendrotoxin; D004247:DNA