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...
