Publication
Regulated fusion of small synaptic vesicles and the ensuing release of neurotransmitter at nerve terminals underlies chemical synaptic transmission between neurons. This process of exocytosis is initiated by an increase in the intracellular Ca2+ concentration caused by the opening of presynaptic Ca2+ channels. Because the intracellular Ca2+ signal that drives vesicle fusion is an extremely short-lived microdomain signal close to open Ca2+ channels which cannot be measured directly, most information on how intracellular Ca2+ triggers vesicle fusion has been obtained by Ca2+ uncaging experiments in nerve terminals and secretory cells. These measurements have shown that an intracellular Ca2+ concentration ([Ca2+]i) signal of approximately 10–30μM induces physiological release responses in many synapses, but the intracellular Ca2+ requirements can differ between secretory systems. The action of Ca2+ in triggering vesicle fusion is highly cooperative over a wide range of [Ca2+]i. The high cooperativity (four or five Ca2+ ions) can cause a strong amplification of transmitter output with even small changes in local [Ca2+]i signaling, and this supralinearity is an important mediator of short-term plasticity of synaptic strength.