TY - JOUR
T1 - Presynaptic cav1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells
AU - Sheets, Lavinia
AU - Kindt, Katie S.
AU - Nicolson, Teresa
PY - 2012/11/28
Y1 - 2012/11/28
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84870171980&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.3005-12.2012
DO - 10.1523/JNEUROSCI.3005-12.2012
M3 - Article
C2 - 23197719
AN - SCOPUS:84870171980
SN - 0270-6474
VL - 32
SP - 17273
EP - 17286
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 48
ER -