Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release

Neuron. 2005 Nov 23;48(4):547-54. doi: 10.1016/j.neuron.2005.09.006.


Ca(2+) triggers neurotransmitter release in at least two principal modes, synchronous and asynchronous release. Synaptotagmin 1 functions as a Ca(2+) sensor for synchronous release, but its role in asynchronous release remains unclear. We now show that in cultured cortical neurons stimulated at low frequency (<or.1 Hz), deletion of synaptotagmin 1 blocks synchronous GABA and glutamate release without significantly increasing asynchronous release. At higher stimulation frequencies (>or Hz), deletion of synaptotagmin 1 also alters only synchronous, not asynchronous, release during the stimulus train, but dramatically enhances "delayed asynchronous release" following the stimulus train. Thus synaptotagmin 1 functions as an autonomous Ca(2+) sensor independent of asynchronous release during isolated action potentials and action potential trains, but restricts asynchronous release induced by residual Ca(2+) after action potential trains. We propose that synaptotagmin 1 occupies release "slots" at the active zone, possibly in a Ca(2+)-independent complex with SNARE proteins that are freed when action potential-induced Ca(2+) influx activates synaptotagmin 1.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium / pharmacology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Mice
  • Mice, Knockout
  • Nerve Endings / drug effects
  • Nerve Endings / metabolism
  • Neural Inhibition / physiology
  • Neurons / physiology
  • Neurotransmitter Agents / metabolism*
  • Synapses / metabolism
  • Synapses / physiology
  • Synaptic Transmission / physiology
  • Synaptotagmin I / deficiency
  • Synaptotagmin I / physiology*
  • Time Factors


  • Ionophores
  • Neurotransmitter Agents
  • Synaptotagmin I
  • Egtazic Acid
  • Ionomycin
  • EGTA acetoxymethyl ester
  • Calcium