title: Fine Tuning of CaV1.3 Ca2+ channel properties in adult inner hair cells positioned in the most sensitive region of the Gerbil Cochlea.
abstract: Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca(2+) inflow through Ca(V)1.3 (L-type) Ca(2+) channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca(2+) currents in IHCs positioned at the middle turn (frequency ∼ 2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na(+) based extracellular solution), we found that the macroscopic Ca(2+) current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ∼-18 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca(2+) channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca(2+) channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune Ca(V)1.3 Ca(2+) channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Zampini
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: Department of Otolaryngology, Tübingen Hearing Research Centre, Laboratory of Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Franz
authors.affiliation: Department of Otolaryngology, Tübingen Hearing Research Centre, Laboratory of Molecular Physiology of Hearing, University of Tübingen, Tübingen, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Holley
authors.affiliation: Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Pavia, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Magistretti
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.affiliation: Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Masetto
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003051:Cochlea / Q000166:cytology*; D005089:Exocytosis; D005849:Gerbillinae; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D007477:Ions / Q000737:chemistry; D008564:Membrane Potentials; D018408:Patch-Clamp Techniques; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D007477:Ions; D012964:Sodium