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1 Yale University School of Medicine
* To whom correspondence should be addressed. E-mail: david.zenisek{at}yale.edu.
Ribbon-containing neurons represent a subset of neural cells that undergo graded membrane depolarizations rather than Na+-channel evoked action potentials. Bipolar cells of the retina are one type of ribbon-containing neuron and extensive research has demonstrated kinetically distinct pools of vesicles that are released and replenished in a calcium dependent manner. In this study, we look at the properties of the fastest pool of releasable vesicles in these cells, often referred to as the immediately releasable pool (IRP), to investigate the relationships between vesicle release and calcium channels in these terminals. Using whole-cell capacitance measurements, we monitored exocytosis in response to different magnitude and duration depolarizations with emphasis on physiologically relevant step depolarizations. We find that release rate of the IRP increases super-linearly with membrane potential and that the IRP is sensitive to elevated EGTA concentrations in a membrane potential dependent manner across the physiological range of membrane potentials. Our results are best explained by a model where multiple Ca2+ channels act in concert to drive exocytosis of a single synaptic vesicle. Pooling calcium entering through many calcium channels may be important for reducing stochastic noise in neurotransmitter release associated with the opening of individual calcium channels.
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