Synaptotagmin Function Illuminated

Neurotransmitter release occurs by exocytosis of synaptic vesicles triggered by Ca²⁺ influx through voltage-gated Ca²⁺ channels. It was found many years ago that release shows a steep dependence on extracellular [Ca²⁺] and increases approximately with the fourth power of [Ca²⁺] (Dodge and Rahamimoff, 1967). It was proposed that Ca²⁺ entering through voltage-gated Ca²⁺ channels binds to intracellular Ca²⁺ receptors, which cooperatively control the release of a vesicle (Katz and Miledi, 1967).

The kinetics of exocytosis can be monitored precisely and with high time resolution by whole-cell patch clamp capacitance measurements (Neher and Marty, 1982; Lindau and Neher, 1988) because the increase in membrane area due to vesicle fusion leads to a proportional increase in membrane capacitance. Such capacitance experiments can be conveniently performed in endocrine cells due to their...