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

• Published in: Hearing research Vol. 345; pp. 57 - 68
• Main Authors: Cao, Xiao-Jie, Oertel, Donata
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2017
• Subjects: Animals; Auditory Pathways - cytology; Auditory Pathways - drug effects; Auditory Pathways - metabolism; Cochlear Nucleus - cytology; Cochlear Nucleus - drug effects; Cochlear Nucleus - metabolism; Gene Expression Regulation; Genetic compensation; Genotype; HCN; Homeostasis; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - antagonists & inhibitors; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - deficiency; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - genetics; KCNA; Kv1.1 Potassium Channel - antagonists & inhibitors; Kv1.1 Potassium Channel - deficiency; Kv1.1 Potassium Channel - genetics; Membrane Potentials - drug effects; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Neuronal Plasticity; Patch-Clamp Techniques; Phenotype; Potassium Channel Blockers - pharmacology; Potassium Channels - deficiency; Potassium Channels - genetics; Time Factors; Ventral cochlear nucleus; Voltage-gated ion channels; Homeostasis; KCNA; HCN; Voltage-gated ion channels; Genetic compensation; Ventral cochlear nucleus
• DOI: 10.1016/j.heares.2017.01.001
• ISSN: 0378-5955; 1878-5891

Low-voltage-activated K+ (gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKL and 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, gKL and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKL and gh also 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 gh and gKL varied 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 gKL and gh. Third, IKL has 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, Ih and IKL are 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 gh and gKL. The independence of resting potentials on gKL and gh shows that gKL and gh do 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 gKL and gh. •The large size of gh and gKL in octopus cells allowed us to resolve and measure Ih and IKL at the resting potential.•Perturbing the magnitude and subunit composition of these conductances genetically did not affect average resting potentials.•IKL balanced Ih at rest in all octopus cells, regardless of mouse strain and individual resting potential.•Instead of gh and gKL regulating the resting potential, it seems that the resting potential regulates gh and gKL.