title: Functional maturation of the exocytotic machinery at gerbil hair cell ribbon synapses.
abstract: Auditory afferent fibre activity in mammals relies on neurotransmission at hair cell ribbon synapses. Developmental changes in the Ca(2+) sensitivity of the synaptic machinery allow inner hair cells (IHCs), the primary auditory receptors, to encode Ca(2+) action potentials (APs) during pre-hearing stages and graded receptor potentials in adult animals. However, little is known about the time course of these changes or whether the kinetic properties of exocytosis differ as a function of IHC position along the immature cochlea. Furthermore, the role of afferent transmission in outer hair cells (OHCs) is not understood. Calcium currents and exocytosis (measured as membrane capacitance changes: DeltaC(m)) were measured with whole-cell recordings from immature gerbil hair cells using near-physiological conditions. The kinetics, vesicle pool depletion and Ca(2+) coupling of exocytosis were similar in apical and basal immature IHCs. This could indicate that possible differences in AP activity along the immature cochlea do not require synaptic specialization. Neurotransmission in IHCs became mature from postnatal day 20 (P20), although changes in its Ca(2+) dependence occurred at P9-P12 in basal and P12-P15 in apical cells. OHCs showed a smaller DeltaC(m) than IHCs that was reflected by fewer active zones in OHCs. Otoferlin, the proposed Ca(2+) sensor in cochlear hair cells, was similarly distributed in both cell types despite the high-order exocytotic Ca(2+) dependence in IHCs and the near-linear relation in OHCs. The results presented here provide a comprehensive study of the function and development of hair cell ribbon synapses.
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.forename: Christoph
authors.initials: C
authors.lastname: Franz
authors.forename: Marlies
authors.initials: M
authors.lastname: Knipper
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000033:anatomy & histology / Q000254:growth & development / Q000294:innervation; D007758:Ear, Inner / Q000254:growth & development* / Q000294:innervation; D004594:Electrophysiology; D005089:Exocytosis / Q000502:physiology*; D005849:Gerbillinae; D006199:Hair Cells, Auditory, Inner / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000502:physiology*; D007150:Immunohistochemistry; D007700:Kinetics; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018377:Neurotransmitter Agents; D002118:Calcium