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Patch-clamp capacitance measurements can monitor in real time the kinetics of exocytosis and endocytosis in living cells. We review the application of this technique to the giant presynaptic terminals of goldfish bipolar cells. These terminals secrete glutamate via the fusion of small, clear-core vesicles at specialized, active zones of release called synaptic ribbons. We compare the functional characteristics of transmitter release at ribbon-type and conventional synapses, both of which have a unique capacity for fast and focal vesicle fusion. Subsequent rapid retrieval and recycling of fused synaptic vesicle membrane allow presynaptic terminals to function independently of the cell soma and, thus, as autonomous computational units. Together with the mobilization of reserve vesicle pools, local cycling of synaptic vesicles may delay the onset of vesicle pool depletion and sustain neuronal output during high stimulation frequencies.
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Recent publications were reviewed as the paper went to press.
Two recent publication that bear directly on the subject of this review appeared after completion of the manuscript. First, optical monitoring of exocytosis with FM dyes has revealed both continuous and transient modes of exocytosis in bipolar-cell terminals (135). During a 6 s depolarization, a phasic burst of exocytosis increased the surface area of the terminal by a maximum of 12%, corresponding to the fusion of 13,000 vesicles. This agrees remarkably well with the total cumulative increase in capacitance following a train of pulses lasting several seconds (approximately 300 fF, corresponding to 12,000 vesicles; Reference 121). Interestingly, endocytosis was inhibited during the depolarization and resumed only after Ca concentration had begun to fall back to the baseline, which again agrees with conclusions from capacitance measurements (118). Second, different types of FM dye were used, together with a destaining model, to reveal fast endocytosis (τ = 5 s) in conventional synaptic boutons (136), comparable in speed to the rapid endocytosis described using capacitance measurements in bipolar cell terminals (117).
135. Rouze NC, Schwartz EA. 1998. Continuous and transient vesicle cycling at a ribbon synapse. J. Neurosci. 18:8614–24
136. Klingauf J, Kavalali ET, Tsien RW. 1998. Kinetics and regulation of fast endocytosis at hippocampal synapses. Nature 394:581–85