title: Functional significance of K+ channel β-subunit KCNE3 in auditory neurons.
abstract: The KCNE3 β-subunit interacts with and regulates the voltage-dependent gating, kinetics, and pharmacology of a variety of Kv channels in neurons. Because a single neuron may express multiple KCNE3 partners, it is impossible to predict the overall functional relevance of the single transmembrane domain peptide on the pore-forming K(+) channel subunits with which it associates. In the inner ear, the role of KCNE3 is undefined, despite its association with Meniere disease and tinnitus. To gain insights on the functional significance of KCNE3 in auditory neurons, we examined the properties of spiral ganglion neurons (SGNs) in Kcne3 null mutant neurons relative to their age-matched controls. We demonstrate that null deletion of Kcne3 abolishes characteristic wide variations in the resting membrane potentials of SGNs and yields age-dependent alterations in action potential and firing properties of neurons along the contour of the cochlear axis, in comparison with age-matched wild-type neurons. The properties of basal SGNs were markedly altered in Kcne3(-/-) mice compared with the wild-type controls; these include reduced action potential latency, amplitude, and increased firing frequency. Analyses of the underlying conductance demonstrate that null mutation of Kcne3 results in enhanced outward K(+) currents, which is sufficient to explain the ensuing membrane potential changes. Additionally, we have demonstrated that KCNE3 may regulate the activity of Kv4.2 channels in SGNs. Finally, there were developmentally mediated compensatory changes that occurred such that, by 8 weeks after birth, the electrical properties of the null mutant neurons were virtually indistinguishable from the wild-type neurons, suggesting that ion channel remodeling in auditory neurons progresses beyond hearing onset.
authors.affiliation: From the Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China, the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Wenying
authors.initials: W
authors.lastname: Wang
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Victor
authors.initials: V
authors.lastname: Wong
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Choong-Ryoul
authors.initials: CR
authors.lastname: Sihn
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and the Department of Pharmacology, Hebei Medical University, Shijiazhuang 050017, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lv
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Perez Flores
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Mousavi-Nik
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and.
authors.forename: Karen Jo
authors.initials: KJ
authors.lastname: Doyle
authors.affiliation: From the Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China, yanfangxu@hotmail.com.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: the Department of Anesthesiology and Pain Medicine, Program in Communication and Sensory Sciences, University of California at Davis School of Medicine, Davis, California 95618, and enyamoah@ucdavis.edu.
authors.forename: Ebenezer N
authors.initials: EN
authors.lastname: Yamoah
mesh_terms: D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D017353:Gene Deletion; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000502:physiology; D013136:Spiral Ganglion / Q000166:cytology* / Q000254:growth & development
chemical_list: C498827:Kcne3 protein, mouse; D024642:Potassium Channels, Voltage-Gated
keywords: Auditory Neuron; Deafness; Gene Knock-out; Hearing; KCNE Subunits; Neurobiology; Neurochemistry; Potassium Channels
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