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

摘要

Low-voltage-activated K+ (g(KL)) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, I-KL and l(h), 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, g(KL). and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting g(KL) 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 g(KL) 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 get and gh. Third, In has two components, one being cc-dendrotoxin (alpha-DTX)-sensitive and partially inactivating and the other being alpha-DTX-insensitive, tetraethylammonium (TEA) -sensitive, and non inactivating. Fourth, the loss of Kv1.1 results in diminution of the alpha-DTX-sensitive In, and compensatory increased expression of an alpha-DTX-insensitive, tetraethylammonium (TEA)-sensitive I-KL. Fifth, I-h and I-KL 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 g(KL) The independence of resting potentials on g(KL) and gh shows that g(KL) 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 g(KL) and gh. (C) 2017 Elsevier B.V. All rights reserved.