title: The role of BKCa channels in electrical signal encoding in the mammalian auditory periphery.
abstract: Large-conductance voltage- and Ca(2+)-activated K+ channels (BKCa) are involved in shaping spiking patterns in many neurons. Less is known about their role in mammalian inner hair cells (IHCs), mechanosensory cells with unusually large BKCa currents. These currents may be involved in shaping the receptor potential, implying crucial importance for the properties of afferent auditory signals. We addressed the function of BKCa by recording sound-induced responses of afferent auditory nerve (AN) fibers from mice with a targeted deletion of the pore-forming alpha-subunit of BKCa (BKalpha(-/-)) and comparing these with voltage responses of current-clamped IHCs. BKCa-mediated currents in IHCs were selectively abolished in BKalpha(-/-), whereas cochlear physiology was essentially normal with respect to cochlear sensitivity and frequency tuning.BKalpha(-/-) AN fibers showed deteriorated precision of spike timing, measured as an increased variance of first spike latency in response to tone bursts. This impairment could be explained by a slowed voltage response in the presynaptic IHC resulting from the reduced K+ conductance in the absence of BKCa. Maximum spike rates of AN fibers were reduced nearly twofold in BKalpha(-/-), contrasting with increased voltage responses of IHCs. In addition to presynaptic changes, which may be secondary to a modest depolarization of BKalpha(-/-) IHCs, this reduction in AN rates suggests a role of BKCa in postsynaptic AN neurons, which was supported by increased refractory periods. In summary, our results indicate an essential role of IHC BKCa channels for precise timing of high-frequency cochlear signaling as well as a function of BKCa in the primary afferent neuron.
authors.affiliation: Physiologisches Institut, Universität Freiburg, D-79104 Freiburg, Germany. dominik.oliver@physiologie.uni-freiburg.de
authors.forename: Dominik
authors.initials: D
authors.lastname: Oliver
authors.forename: Annette M
authors.initials: AM
authors.lastname: Taberner
authors.forename: Henrike
authors.initials: H
authors.lastname: Thurm
authors.forename: Matthias
authors.initials: M
authors.lastname: Sausbier
authors.forename: Claudia
authors.initials: C
authors.lastname: Arntz
authors.forename: Peter
authors.initials: P
authors.lastname: Ruth
authors.forename: Bernd
authors.initials: B
authors.lastname: Fakler
authors.forename: M Charles
authors.initials: MC
authors.lastname: Liberman
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials; D000818:Animals; D003051:Cochlea / Q000502:physiology; D003056:Cochlear Nerve / Q000166:cytology / Q000502:physiology*; D004056:Differential Threshold; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012032:Refractory Period, Electrophysiological; D013997:Time Factors
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D020033:Protein Isoforms