Ca2+-dependent mechanisms of presynaptic control at central synapses

Neuroscientist. 2006 Aug;12(4):317-26. doi: 10.1177/1073858405284672.


Classically, a high-power association relates the neurotransmitter release probability to the concentration of presynaptic Ca2+. Activated by the action potential waveform, voltage-gated Ca2+ channels mediate Ca2+entry into presynaptic terminals. Inside the terminal, Ca2+ ions rapidly bind to endogenous intracellular buffers and could trigger Ca2+ release from internal Ca2+ stores. The resulting space-time profile of free Ca2+ determines the time course and probability of neurotransmitter release through the interaction with molecular release triggers strategically located in the vicinity of release sites. Following a rapid concentration transient, excess Ca2+ has to be removed from the cytosol through the process involving Ca2+ uptake by the endoplasmatic reticulum stores, sequestration by mitochondria, and/or extrusion into the extracellular medium. The ongoing synaptic activity could affect any of the multiple factors that shape presynaptic Ca2+ dynamics, thus arbitrating use-dependent modification of the neurotransmitter release probability. Here we present an overview of major players involved in Ca2+-dependent presynaptic regulation of neurotransmitter release and discuss the relationships arising between their actions.

Publication types

  • Review

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / physiology
  • Central Nervous System / physiology*
  • Humans
  • Neurotransmitter Agents / metabolism*
  • Presynaptic Terminals / metabolism*
  • Signal Transduction / physiology*
  • Synapses / metabolism*


  • Calcium Channels
  • Neurotransmitter Agents
  • Calcium