title: Functional contributions of HCN channels in the primary auditory neurons of the mouse inner ear.
abstract: The hyperpolarization-activated current, Ih, is carried by members of the Hcn channel family and contributes to resting potential and firing properties in excitable cells of various systems, including the auditory system. Ih has been identified in spiral ganglion neurons (SGNs); however, its molecular correlates and their functional contributions have not been well characterized. To investigate the molecular composition of the channels that carry Ih in SGNs, we examined Hcn mRNA harvested from spiral ganglia of neonatal and adult mice using quantitative RT-PCR. The data indicate expression of Hcn1, Hcn2, and Hcn4 subunits in SGNs, with Hcn1 being the most highly expressed at both stages. To investigate the functional contributions of HCN subunits, we used the whole-cell, tight-seal technique to record from wild-type SGNs and those deficient in Hcn1, Hcn2, or both. We found that HCN1 is the most prominent subunit contributing to Ih in SGNs. Deletion of Hcn1 resulted in reduced conductance (Gh), slower activation kinetics (τfast), and hyperpolarized half-activation (V1/2) potentials. We demonstrate that Ih contributes to SGN function with depolarized resting potentials, depolarized sag and rebound potentials, accelerated rebound spikes after hyperpolarization, and minimized jitter in spike latency for small depolarizing stimuli. Auditory brainstem responses of Hcn1-deficient mice showed longer latencies, suggesting that HCN1-mediated Ih is critical for synchronized spike timing in SGNs. Together, our data indicate that Ih contributes to SGN membrane properties and plays a role in temporal aspects of signal transmission between the cochlea and the brain, which are critical for normal auditory function.
authors: Neuroscience Graduate Program, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors: Ye-Hyun
authors: YH
authors: Kim
authors: Jeffrey R
authors: JR
authors: Holt
mesh_terms: D000200:Action Potentials; D000818:Animals; D001933:Brain Stem / Q000502:physiology; D005072:Evoked Potentials, Auditory; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D013136:Spiral Ganglion / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
chemical_list: D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D012333:RNA, Messenger
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