Regulation of presynaptic Ca(V)2.1 channels by Ca2+ sensor proteins mediates short-term synaptic plasticity

Neuron. 2008 Jan 24;57(2):210-6. doi: 10.1016/j.neuron.2007.11.036.


Short-term synaptic plasticity shapes the postsynaptic response to bursts of impulses and is crucial for encoding information in neurons, but the molecular mechanisms are unknown. Here we show that activity-dependent modulation of presynaptic Ca(V)2.1 channels mediated by neuronal Ca(2+) sensor proteins (CaS) induces synaptic plasticity in cultured superior cervical ganglion (SCG) neurons. A mutation of the IQ-like motif in the C terminus that blocks Ca(2+)/CaS-dependent facilitation of the P/Q-type Ca(2+) current markedly reduces facilitation of synaptic transmission. Deletion of the nearby calmodulin-binding domain, which inhibits CaS-dependent inactivation, substantially reduces depression of synaptic transmission. These results demonstrate that residual Ca(2+) in presynaptic terminals can act through CaS-dependent regulation of Ca(V)2.1 channels to induce short-term synaptic facilitation and rapid synaptic depression. Activity-dependent regulation of presynaptic Ca(V)2.1 channels by CaS proteins may therefore be a primary determinant of short-term synaptic plasticity and information-processing in the nervous system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / physiology
  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, N-Type / physiology*
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Intracellular Calcium-Sensing Proteins / physiology*
  • Mice
  • Microinjections / methods
  • Mutation
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Neurons / cytology*
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / physiology*
  • Superior Cervical Ganglion / cytology
  • Time Factors
  • omega-Agatoxin IVA / pharmacology


  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Intracellular Calcium-Sensing Proteins
  • omega-Agatoxin IVA
  • voltage-dependent calcium channel (P-Q type)
  • Calcium