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Abstract

Transmitter release is triggered by highly localized, transient increases in the presynaptic Ca²⁺ concentration ([Ca²⁺]). Rapidly decaying [Ca²⁺] elevations were generated using Ca²⁺ uncaging techniques, and [Ca²⁺] was measured with a low-affinity Ca²⁺ indicator in a giant presynaptic terminal, the calyx of Held, in rat brain slices. The rise time and amplitude of evoked excitatory postsynaptic currents (EPSCs) depended on the half-width of the fluorescence transient, which was predicted by a five-binding site model of a Ca²⁺ sensor having relatively high affinity (Kd approx13 muM). Very fast [Ca²⁺] transients (half-width <0.5 ms) evoked EPSCs similar to those elicited by a single action potential (AP) in the same synapse. Triggering release with dual [Ca²⁺] transients of variable amplitudes demonstrated the supralinear transfer function of the sensor. The sensitivity of release to the time course of the [Ca²⁺] transient may contribute to mechanisms by which the presynaptic AP waveform controls synaptic strength.