Mechanisms contributing to synaptic Ca2+ signals and their heterogeneity in hair cells
Thomas Frank, Darina Khimich, Andreas Neef, and Tobias Moser (2009)
PNAS 106(11):4483-4488. ( BibTeX export )
Sound coding at hair cell ribbon synapses is tightly regulated by Ca2+. Here, we used patch-clamp, fast confocal Ca2+ imaging and modeling to characterize synaptic Ca2+ signaling in cochlear inner hair cells (IHCs) of hearing mice. Submicrometer fluorescence hotspots built up and collapsed at the base of IHCs within a few milliseconds of stimulus onset and cessation. They most likely represented Ca2+ microdomains arising from synaptic Ca2+ influx through CaV1.3 channels. Synaptic Ca2+ microdomains varied substantially in amplitude and voltage dependence even within single IHCs. Testing putative mechanisms for the heterogeneity of Ca2+ signaling, we found the amplitude variability unchanged when blocking mitochondrial Ca2+ uptake or Ca2+-induced Ca2+ release, buffering cytosolic Ca2+ by millimolar concentrations of EGTA, or elevating the Ca2+ channel open probability by the dihydropyridine agonist BayK8644. However, we observed substantial variability also for the fluorescence of immunolabeled CaV1.3 Ca2+ channel clusters. Moreover, the Ca2+ microdomain amplitude correlated positively with the size of the corresponding synaptic ribbon. Ribbon size, previously suggested to scale with the number of synaptic Ca2+ channels, was approximated by using fluorescent peptide labeling. We propose that IHCs adjust the number and the gating of CaV1.3 channels at their active zones to diversify their transmitter release rates.
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