Calcium-dependent interaction of N-type calcium channels with the synaptic core complex

Nature. 1996 Feb 1;379(6564):451-4. doi: 10.1038/379451a0.


Neurotransmitter release is initiated by influx of Ca2+ through voltage-gated Ca2+ channels, within 200 microseconds of the action potential arriving at the synaptic terminal, as the Ca2+ concentration increases from 100 nM to > 200 microM. Exocytosis requires high Ca2+ concentration, with a threshold of 20-50 microM and half-maximal activation at 190 microM. The synaptic membrane proteins syntaxin, 25K synaptosome-associated protein (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin, are thought to form a synaptic core complex which mediates vesicle docking and membrane fusion. Synaptotagmin may be the low-affinity Ca(2+)-sensor, but other Ca(2+)-sensors are involved as residual neurotransmission persists in synaptotagmin-null mutants. Syntaxin binds to N-type Ca2+ channels at a site in the intracellular loop connecting domains II and III. Here we describe Ca(2+)-dependent interaction of this site with syntaxin and SNAP25 which has a biphasic dependence on Ca2+, with maximal binding at 20 microM free Ca2+, near the threshold for transmitter release. Ca(2+)-dependent interaction of Ca2+ channels with the synaptic core complex may be important for Ca(2+)-dependent docking and fusion of synaptic vesicles.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium-Binding Proteins*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism
  • Qa-SNARE Proteins
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Synapses / metabolism*
  • Synaptic Vesicles / metabolism
  • Synaptosomal-Associated Protein 25
  • Synaptotagmins


  • Calcium Channels
  • Calcium-Binding Proteins
  • Membrane Glycoproteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Qa-SNARE Proteins
  • Recombinant Fusion Proteins
  • Snap25 protein, rat
  • Synaptosomal-Associated Protein 25
  • Synaptotagmins
  • Calcium