title: Heterogeneous intrinsic excitability of murine spiral ganglion neurons is determined by Kv1 and HCN channels.
abstract: The spiral ganglion conveys afferent auditory information predominantly through a single class of type I neurons that receive signals from inner hair cell sensory receptors. These auditory primary afferents, like in other systems (Puopolo and Belluzzi, 1998; Gascon and Moqrich, 2010; Leao et al., 2012) possess a marked diversity in their electrophysiological features (Taberner and Liberman, 2005). Consistent with these observations, when the auditory primary afferents were assessed in neuronal explants separated from their peripheral and central targets it was found that individual neurons were markedly heterogeneous in their endogenous electrophysiological features. One aspect of this heterogeneity, obvious throughout the ganglion, was their wide range of excitability as assessed by voltage threshold measurements (Liu and Davis, 2007). Thus, while neurons in the base differed significantly from apical and middle neurons in their voltage thresholds, each region showed distinctly wide ranges of values. To determine whether the resting membrane potentials (RMPs) of these neurons correlate with the threshold distribution and to identify the ion channel regulatory elements underlying heterogeneous neuronal excitability in the ganglion, patch-clamp recordings were made from postnatal day (P5-8) murine spiral ganglion neurons in vitro. We found that RMP mirrored the tonotopic threshold distribution, and contributed an additional level of heterogeneity in each cochlear location. Pharmacological experiments further indicated that threshold and RMP was coupled through the Kv1 current, which had a dual impact on both electrophysiological parameters. Whereas, hyperpolarization-activated cationic channels decoupled these two processes by primarily affecting RMP without altering threshold level. Thus, beyond mechanical and synaptic specializations, ion channel regulation of intrinsic membrane properties imbues spiral ganglion neurons with different excitability levels, a feature that contributes to primary auditory afferent diversity.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Rutgers University, New Jersey Medical School, Newark, NJ 07746, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA. Electronic address: rldavis@rci.rutgers.edu.
authors.forename: R L
authors.initials: RL
authors.lastname: Davis
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena / Q000187:drug effects; D001703:Biophysics; D019256:Cadmium Chloride / Q000494:pharmacology; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism*; D013136:Spiral Ganglion / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004546:Elapid Venoms; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D051637:Shaker Superfamily of Potassium Channels; D013779:Tetrodotoxin; C020273:dendrotoxin; D015761:4-Aminopyridine; D019256:Cadmium Chloride
keywords: 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid; 4-AP; 4-aminopyridine; ANOVA; CdCl(2); CsCl; DIV; DTX; EGTA; EPSP; HCN; HEPES; I(h); IHC; K(v)1; PBS; RMP; SA; SR; TEA; TTX; V(θ); analysis of variance; auditory; cadmium chloride; cesium chloride; days in vitro; dendrotoxin; ethylene glycol tetraacetic acid; excitatory postsynaptic potential; hyperpolarization-activated cationic channel; hyperpolarization-activated cationic current; inner hair cell; intrinsic excitability; phosphate-buffered saline; resting membrane potential; slowly accommodating; spiral ganglion neuron; spontaneous discharge rate; tetraethylammonium; tetrodotoxin; voltage threshold