Nature 371, 513 - 515 (06 October 1994); doi:10.1038/371513a0

Calcium dependence of the rate of exocytosis in a synaptic terminal

Ruth Heidelberger, Christian Heinemann, Erwin Neher & Gary Matthews^*

Abteilung Membranbiophysik, Max-Planck-lnstitut für biophysikalische Chemie, Am Faberg, 37077 Göttingen, Germany
^* Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York 11794-5230, USA

RAPID calcium-dependent exocytosis underlies neurotransmitter release from nerve terminals. Despite the fundamental importance of this process, neither the relationship between presynaptic intra-cellular calcium ion concentration ([Ca²⁺]_i) and rate of exocytosis, nor the maximal rate of secretion is known quantitatively. To provide this information, we have used flash photolysis of caged Ca²⁺ to elevate [Ca²⁺]_i rapidly and uniformly in synaptic terminals, while measuring membrane capacitance as an index of exocytosis and monitoring [Ca²⁺]_i with a Ca²⁺-indicator dye. When [Ca²⁺]_i was abruptly increased to >10 M, capacitance rose at a rate that increased steeply with [Ca²⁺]_i. The steepness suggested that at least four calcium ions must bind to activate synaptic vesicle fusion. Half-saturation was at 194 M, and the maximal rate constant was 2,000–3,000 s^–1. A given synaptic vesicle can exocytose with high probability within a few hundred microseconds, if [Ca²⁺]_i rises above lOOM. These properties provide for the extremely rapid signalling required for neuronal communication.

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