title: Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus.
abstract: Low-voltage-activated K+(gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKLand Ih, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, gKLand ghcontribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKLand ghalso affect the coupling of somatic depolarization with the generation of action potentials. To learn how these important conductances are regulated we have investigated how genetic perturbations affect their expression in octopus cells of the ventral cochlear nucleus (VCN). We report five new findings: First, the magnitude of ghand gKLvaried over more than two-fold between wild type strains of mice. Second, average resting potentials are not different in different strains of mice even in the face of large differences in average gKLand gh. Third, IKLhas two components, one being α-dendrotoxin (α-DTX)-sensitive and partially inactivating and the other being α-DTX-insensitive, tetraethylammonium (TEA)-sensitive, and non-inactivating. Fourth, the loss of Kv1.1 results in diminution of the α-DTX-sensitive IKL, and compensatory increased expression of an α-DTX-insensitive, tetraethylammonium (TEA)-sensitive IKL. Fifth, Ihand IKLare balanced at the resting potential in all wild type and mutant octopus cells even when resting potentials vary in individual cells over nearly 10 mV, indicating that the resting potential influences the expression of ghand gKL. The independence of resting potentials on gKLand ghshows that gKLand ghdo not, over days or weeks, determine the resting potential but rather that the resting potential plays a role in regulating the magnitude of either or both gKLand gh.
authors.affiliation: Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Cao
authors.affiliation: Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA. Electronic address: doertel@wisc.edu.
authors.forename: Donata
authors.initials: D
authors.lastname: Oertel
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017626:Cochlear Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D008564:Membrane Potentials / Q000187:drug effects; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D010641:Phenotype; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000172:deficiency / Q000235:genetics*; D013997:Time Factors
chemical_list: C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; C496947:Kcna1 protein, mouse; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D051662:Kv1.1 Potassium Channel
keywords: Genetic compensation; HCN; Homeostasis; KCNA; Ventral cochlear nucleus; Voltage-gated ion channels