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A puzzling property of synaptic transmission, originally established at the neuromuscular junction, is that the time course of transmitter release is independent of the extracellular Ca 2+  concentration ([Ca 2+ ] o ), whereas the rate of release is highly [Ca 2+ ] o -dependent. Here, we examine the time course of release at inhibitory basket cell-Purkinje cell synapses and show that it is independent of [Ca 2+ ] o . Modeling of Ca 2+ -dependent transmitter release suggests that the invariant time course of release critically depends on tight coupling between Ca 2+  channels and release sensors. Experiments with exogenous Ca 2+  chelators reveal that channel-sensor coupling at basket cell-Purkinje cell synapses is very tight, with a mean distance of 10–20 nm. Thus, tight channel-sensor coupling provides a mechanistic explanation for the apparent [Ca 2+ ] o  independence of the time course of release.

Nanodomain coupling explains Ca 2+ independence of transmitter release time course at a fast central synapse