Interactions between presynaptic Ca2+ channels, cytoplasmic messengers and proteins of the synaptic vesicle release complex

Trends Pharmacol Sci. 2001 Oct;22(10):519-25. doi: 10.1016/s0165-6147(00)01800-9.


Influx of Ca(2+) through presynaptic voltage-gated Ca(2+) channels is a key step in rapid neurotransmitter release. The amount of Ca(2+) entering through these channels is modulated by a plethora of intracellular messenger molecules, including betagamma-subunits of G proteins, and protein kinases. In addition, Ca(2+) channels bind physically to proteins of the vesicle-release machinery in a Ca(2+)-dependent manner, which can, in turn, regulate the activity of Ca(2+) channels. Recent evidence suggests that second messengers and presynaptic vesicle-release proteins do not regulate Ca(2+) channel activity as independent entities, but that there is extensive crosstalk between these two mechanisms. The complex interactions between second messengers, vesicle-release proteins and voltage-gated Ca(2+) channels might provide multiple avenues for fine-tuning Ca(2+) entry into the presynaptic terminal and, consequently, neurotransmission.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / metabolism*
  • Cytoplasm / metabolism*
  • Humans
  • Membrane Proteins / metabolism*
  • Presynaptic Terminals / metabolism*
  • SNARE Proteins
  • Second Messenger Systems / physiology*
  • Synaptic Vesicles / metabolism*
  • Vesicular Transport Proteins*


  • Calcium Channels
  • Membrane Proteins
  • SNARE Proteins
  • Vesicular Transport Proteins
  • Calcium