Calcium Cooperativity of Exocytosis as a Measure of Calcium Channel Domain Overlap

Victor Matveev, Richard Bertram, Arthur Sherman

The number of calcium channels contributing to the exocytosis of a single neurotransmitter vesicle in a presynaptic terminal has been a question of significant interest and debate, and is important for a full understanding of localized calcium signaling in general, and synaptic physiology in particular. This is usually estimated by measuring the sensitivity of the neurotransmitter release rate to changes in the synaptic calcium current, which is varied using appropriate voltage-clamp protocols or via pharmacological calcium channel block under the condition of constant single-channel calcium current. The slope of the resulting log-log plot of transmitter release rate versus presynaptic calcium current is termed calcium current cooperativity of exocytosis, and provides indirect information about the underlying presynaptic morphology. In this review, we discuss the relationship between the calcium current cooperativity and the average number of calcium channels participating in the exocytosis of a single vesicle, termed the calcium channel cooperativity. We relate these quantitites to the morphology of the presynaptic active zone. We also review experimental studies of calcium current cooperativity and its modulation during development in different classes of synapses.