TY - JOUR
T1 - Sharp Ca 2+ Nanodomains beneath the ribbon promote highly synchronous multivesicular release at hair cell synapses
AU - Graydon, Cole W.
AU - Cho, Soyoun
AU - Li, Geng Lin
AU - Kachar, Bechara
AU - von Gersdorff, Henrique
PY - 2011/11/16
Y1 - 2011/11/16
N2 - Hair cell ribbon synapses exhibit several distinguishing features. Structurally, a dense body, or ribbon, is anchored to the presynaptic membrane and tethers synaptic vesicles; functionally, neurotransmitter release is dominated by large EPSC events produced by seemingly synchronous multivesicular release. However, the specific role of the synaptic ribbon in promoting this form of release remains elusive. Using complete ultrastructural reconstructions and capacitance measurements of bullfrog amphibian papilla hair cells dialyzed with high concentrations of a slow Ca 2+ buffer (10 mM EGTA), we found that the number of synaptic vesicles at the base of the ribbon correlated closely to those vesicles that released most rapidly and efficiently, while the rest of the ribbon-tethered vesicles correlated to a second, slower pool of vesicles. Combined with the persistence of multivesicular release in extreme Ca 2+ buffering conditions (10 mM BAPTA), our data argue against the Ca 2+-dependentcompoundfusion of ribbon-tethered vesicles at hair cell synapses. Moreover, during hair cell depolarization, our results suggest that elevated Ca 2+ levels enhance vesicle pool replenishment rates. Finally, using Ca 2+ diffusion simulations, we propose that the ribbon and its vesicles define a small cytoplasmic volume where Ca 2+ buffer is saturated, despite 10 mM BAPTA conditions. This local buffer saturation permits fast and large Ca 2+ rises near release sites beneath the synaptic ribbon that can trigger multiquantal EPSCs.Weconclude that, by restricting the available presynaptic volume, the ribbonmaybe creating conditions for the synchronous release of a small cohort of docked vesicles.
AB - Hair cell ribbon synapses exhibit several distinguishing features. Structurally, a dense body, or ribbon, is anchored to the presynaptic membrane and tethers synaptic vesicles; functionally, neurotransmitter release is dominated by large EPSC events produced by seemingly synchronous multivesicular release. However, the specific role of the synaptic ribbon in promoting this form of release remains elusive. Using complete ultrastructural reconstructions and capacitance measurements of bullfrog amphibian papilla hair cells dialyzed with high concentrations of a slow Ca 2+ buffer (10 mM EGTA), we found that the number of synaptic vesicles at the base of the ribbon correlated closely to those vesicles that released most rapidly and efficiently, while the rest of the ribbon-tethered vesicles correlated to a second, slower pool of vesicles. Combined with the persistence of multivesicular release in extreme Ca 2+ buffering conditions (10 mM BAPTA), our data argue against the Ca 2+-dependentcompoundfusion of ribbon-tethered vesicles at hair cell synapses. Moreover, during hair cell depolarization, our results suggest that elevated Ca 2+ levels enhance vesicle pool replenishment rates. Finally, using Ca 2+ diffusion simulations, we propose that the ribbon and its vesicles define a small cytoplasmic volume where Ca 2+ buffer is saturated, despite 10 mM BAPTA conditions. This local buffer saturation permits fast and large Ca 2+ rises near release sites beneath the synaptic ribbon that can trigger multiquantal EPSCs.Weconclude that, by restricting the available presynaptic volume, the ribbonmaybe creating conditions for the synchronous release of a small cohort of docked vesicles.
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U2 - 10.1523/JNEUROSCI.1866-11.2011
DO - 10.1523/JNEUROSCI.1866-11.2011
M3 - Article
C2 - 22090491
AN - SCOPUS:81255143007
SN - 0270-6474
VL - 31
SP - 16637
EP - 16650
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 46
ER -