Mobility of calcium channels in the presynaptic membrane

Neuron. 2015 May 6;86(3):672-9. doi: 10.1016/j.neuron.2015.03.050. Epub 2015 Apr 16.

Abstract

Unravelling principles underlying neurotransmitter release are key to understand neural signaling. Here, we describe how surface mobility of voltage-dependent calcium channels (VDCCs) modulates release probabilities (P(r)) of synaptic vesicles (SVs). Coupling distances of <10 to >100 nm have been reported for SVs and VDCCs in different synapses. Tracking individual VDCCs revealed that within hippocampal synapses, ∼60% of VDCCs are mobile while confined to presynaptic membrane compartments. Intracellular Ca(2+) chelation decreased VDCC mobility. Increasing VDCC surface populations by co-expression of the α2δ1 subunit did not alter channel mobility but led to enlarged active zones (AZs) rather than higher channel densities. VDCCs thus scale presynaptic scaffolds to maintain local mobility. We propose that dynamic coupling based on mobile VDCCs supports calcium domain cooperativity and tunes neurotransmitter release by equalizing Pr for docked SVs within AZs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Animals
  • Cadmium Chloride / pharmacology
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Embryo, Mammalian
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Hippocampus / cytology
  • Models, Biological
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • Potassium Chloride / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / physiology*
  • Presynaptic Terminals / ultrastructure
  • Protein Transport / genetics
  • Protein Transport / physiology*
  • Rats
  • Rats, Wistar
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism
  • Synaptotagmin I / metabolism

Substances

  • Bsn protein, rat
  • Calcium Channel Blockers
  • Calcium Channels
  • Nerve Tissue Proteins
  • Synaptotagmin I
  • Potassium Chloride
  • Cadmium Chloride
  • Calcium