Sheets, L., Kindt, K.S., and Nicolson, T. (2012) Presynaptic CaV1.3 Channels Regulate Synaptic Ribbon Size and Are Required for Synaptic Maintenance in Sensory Hair Cells. The Journal of neuroscience : the official journal of the Society for Neuroscience. 32(48):17273-17286.
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.