Presynaptic cav1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells

Lavinia Sheets, Katie S. Kindt, Teresa Nicolson

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

L-type calcium channels (CaV1) are involved in diverse processes, such as neurotransmission, hormone secretion, muscle contraction, and gene expression. In this study, we uncover a role for CaV1.3a 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 CaV1.3a 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 caV1.3a 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 Ca2+ influx may be used by other cell types, because we observed similar pharmacological effects on pinealocyte synaptic ribbons. Our results indicate that Ca2+ influx through CaV1.3 fine tunes synaptic ribbon size during hair-cell maturation and that CaV1.3 is required for synaptic maintenance.

Original languageEnglish
Pages (from-to)17273-17286
Number of pages14
JournalJournal of Neuroscience
Volume32
Issue number48
DOIs
StatePublished - Nov 28 2012

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