title: Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells.
abstract: L-type calcium channels (Ca(V)1) are involved in diverse processes, such as neurotransmission, hormone secretion, muscle contraction, and gene expression. In this study, we uncover a role for Ca(V)1.3a in regulating the architecture of a cellular structure, the ribbon synapse, in developing zebrafish sensory hair cells. By combining in vivo calcium imaging with confocal and super-resolution structured illumination microscopy, we found that genetic disruption or acute block of Ca(V)1.3a channels led to enlargement of synaptic ribbons in hair cells. Conversely, activating channels reduced both synaptic-ribbon size and the number of intact synapses. Along with enlarged presynaptic ribbons in ca(V)1.3a mutants, we observed a profound loss of juxtaposition between presynaptic and postsynaptic components. These synaptic defects are not attributable to loss of neurotransmission, because vglut3 mutants lacking neurotransmitter release develop relatively normal hair-cell synapses. Moreover, regulation of synaptic-ribbon size by Ca(2+) influx may be used by other cell types, because we observed similar pharmacological effects on pinealocyte synaptic ribbons. Our results indicate that Ca(2+) influx through Ca(V)1.3 fine tunes synaptic ribbon size during hair-cell maturation and that Ca(V)1.3 is required for synaptic maintenance.
authors.affiliation: Howard Hughes Medical Institute, Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Sheets
authors.forename: Katie S
authors.initials: KS
authors.lastname: Kindt
authors.forename: Teresa
authors.initials: T
authors.lastname: Nicolson
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D020746:Calcium Channels, L-Type; D029961:Zebrafish Proteins; C488619:cacna1da protein, zebrafish