title: CaV1.3 channels are essential for development and presynaptic activity of cochlear inner hair cells.
abstract: Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, afferent synaptic transmission is triggered by spontaneous Ca2+ spikes of IHCs, which are under efferent cholinergic control. Around the onset of hearing, large-conductance Ca2+-activated K+ channels are acquired, and Ca2+ spikes as well as the cholinergic innervation are lost. Here, we performed patch-clamp measurements in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of this prevailing voltage-gated Ca2+ channel in IHC development and synaptic function. The small Ca2+ current remaining in IHCs from 3-week-old CaV1.3-/- mice was mainly mediated by L-type Ca2+ channels, because it was sensitive to dihydropyridines but resistant to inhibitors of non-L-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal exocytosis in CaV1.3-/- IHC, which was solely mediated by L-type Ca2+ channels, whereas robust exocytic responses were elicited by photolysis of caged Ca2+. Secretion triggered by short depolarizations was reduced proportionally to the Ca2+ current, suggesting that the coupling of the remaining channels to exocytosis was unchanged. CaV1.3-/- IHCs lacked the Ca2+ action potentials and displayed a complex developmental failure. Most strikingly, we observed a continued presence of efferent cholinergic synaptic transmission and a lack of functional large-conductance Ca2+-activated K+ channels up to 4 weeks after birth. We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission.
authors.affiliation: Department of Otolaryngology, Goettingen University Medical School, 37075 Goettingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brandt
authors.forename: Joerg
authors.initials: J
authors.lastname: Striessnig
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D002469:Cell Separation; D003051:Cochlea / Q000166:cytology* / Q000502:physiology*; D003638:Deafness / Q000235:genetics; D025802:Electric Capacitance; D005089:Exocytosis / Q000502:physiology; D006199:Hair Cells, Auditory, Inner / Q000166:cytology / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D002118:Calcium