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Among voltage\u2010gated channels, hyperpolarization\u2010activated cyclic nucleotide\u2010gated (HCN) channels open with hyperpolarization and depolarize the cell until the resting membrane potential. The functions for hearing are not well elucidated and knowledge about localization is controversial. We created a detailed map of subcellular location and co\u2010expression of all four HCN subunits across different mammalian species including CBA\/J, C57Bl\/6N, Ly5.1 mice, guinea pigs, cats, and human subjects. We correlated age\u2010related hearing deterioration in CBA\/J and C57Bl\/6N with expression levels of HCN1, \u22122, and \u22124 in individual auditory neurons from the same cohort. Spatiotemporal expression during murine postnatal development exposed HCN2 and HCN4 involvement in a critical phase of hair cell innervation. The huge diversity of subunit composition, but lack of relevant heteromeric pairing along the perisomatic membrane and axon initial segments, highlighted an active role for auditory neurons. Neuron clusters were found to be the hot spots of HCN1, \u22122, and \u22124 immunostaining. HCN channels were also located in afferent and efferent fibers of the sensory epithelium. Age\u2010related changes on HCN subtype expression were not uniform among mice and could not be directly correlated with audiometric data. The oldest mice groups revealed HCN channel up\u2010 or downregulation, depending on the mouse strain. The unexpected involvement of HCN channels in outer hair cell function where HCN3 overlaps prestin location emphasized the importance for auditory function. A better understanding may open up new possibilities to tune neuronal responses evoked through electrical stimulation by cochlear implants.<\/jats:p>","DOI":"10.1002\/jnr.24754","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T18:54:31Z","timestamp":1605207271000},"page":"699-728","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age\u2010dependent changes"],"prefix":"10.1002","volume":"99","author":[{"given":"Maria","family":"Luque","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Medical University of Innsbruck Innsbruck 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