Intracellular calcium dependence of transmitter release rates at a fast central synapse


Calcium-triggered fusion of synaptic vesicles and neurotransmitter release are fundamental signalling steps in the central nervous system. It is generally assumed that fast transmitter release is triggered by elevations in intracellular calcium concentration ([Ca2+]i) to at least 100 µM near the sites of vesicle fusion1,2,3,4,5. For synapses in the central nervous system, however, there are no experimental estimates of this local [Ca2+]i signal. Here we show, by using calcium ion uncaging in the large synaptic terminals of the calyx of Held, that step-like elevations to only 10 µM [Ca2+] i induce fast transmitter release, which depletes around 80% of a pool of available vesicles in less than 3 ms. Kinetic analysis of transmitter release rates after [Ca2+]i steps revealed the rate constants for calcium binding and vesicle fusion. These show that transient (around 0.5 ms) local elevations of [Ca2+]i to peak values as low as 25 µM can account for transmitter release during single presynaptic action potentials. The calcium sensors for vesicle fusion are far from saturation at normal release probability. This non-saturation, and the high intracellular calcium cooperativity in triggering vesicle fusion, make fast synaptic transmission very sensitive to modulation by changes in local [Ca2+]i.

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Figure 1: Presynaptic [Ca2+] steps and postsynaptic detection of transmitter release.
Figure 2: [Ca2+]i elevations induced by flashes and presynaptic depolarizations release vesicles from a common pool.
Figure 3: Intracellular Ca2+ concentration dependence of transmitter release rates at the calyx of Held synapse.
Figure 4: The predicted local [Ca2+]i signal at an average Ca2+ sensor for vesicle fusion during single presynaptic action potentials.


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We thank T. Sakaba for discussions, and J. Rettig, M. Casado, P. Ascher and R. Fernández-Chacon for critical comments on the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft.

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Correspondence to Ralf Schneggenburger.

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Schneggenburger, R., Neher, E. Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406, 889–893 (2000).

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