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Synaptic efficacy critically depends on the presynaptic intracellular calcium concentration ([Ca^sup 2+^]^sub i^). We measured the calcium sensitivity of glutamate release in a rat auditory brainstem synapse by laser photolysis of caged calcium. A rise in [Ca^sup 2+^]^sub i^ to 1 micromolar readily evoked release. An increase to >30 micromolar depleted the releasable vesicle pool in <0.5 millisecond. A comparison with action potential-evoked release suggested that a brief increase of [Ca^sup 2+^]^sub i^ to ~10 micromolar would be sufficient to reproduce the physiological release pattern. Thus, the calcium sensitivity of release at this synapse is high, and the distinction between phasic and delayed release is less pronounced than previously thought.
In response to an action potential, the presynaptic release probability is strongly increased for a few milliseconds. This phasic release is thought to be triggered by a brief, localized increase in [Ca^sup 2+^]^sub i^ in the vicinity of open, presynaptic Ca^sup 2+^ channels. The Ca^sup 2+^ sensitivity of phasic release in mammalian central synapses is not yet known. On the basis of results obtained in other synapses, it has been assumed that a low-affinity Ca^sup 2+^ sensor, which is activated by local increases of [Ca^sup 2+^]^sub i^ to >100 (mu)M, triggers phasic release in mammalian central synapses (1-4). In contrast, the more prolonged, delayed release period that, at most synapses, follows the phasic release may be controlled by a separate Ca^sup 2+^ sensor with a much higher affinity for Ca^sup 2+^ (5).
We measured the Ca^sup 2+^ sensitivity of glutamate release at a giant synapse in the auditory brainstem, the axosomatic synapse formed by the calyx of Held with a principal cell in the medial nucleus of the trapezoid body. Using laser photolysis of caged Ca^sup 2+^, we compared in the same terminals release evoked by a sustained, spatially uniform rise in presynaptic [Ca^sup 2+^]^sub i^ (6) with release triggered by action potentials, during which changes in [Ca^sup 2+^]^sub i^ are transient and highly localized (3). In 9-day-old rats, this synapse shows prominent synaptic depression during high-frequency signaling, which is most likely caused by rapid depletion of the releasable pool of vesicles (6-8). In order to relate the flash-evoked excitatory postsynaptic currents (EPSCs) to the size of the releasable pool in the same terminal,...