A new look at calcium channel α2δ subunits

Curr Opin Neurobiol. 2010 Oct;20(5):563-71. doi: 10.1016/j.conb.2010.05.007. Epub 2010 Jun 25.


The classical roles of α(2)δ proteins are as accessory calcium channel subunits, enhancing channel trafficking. They were thought to have type-I transmembrane topology, but we find that they can form GPI-anchored proteins. Moreover α(2)δ-1 and α(2)δ-3 have been shown to have novel functions in synaptogenesis, independent of their effect on calcium channels. In neurons, the α(2)δ-1 subunits are present mainly in presynaptic terminals. Peripheral sensory nerve injury results in the up-regulation of α(2)δ-1 in dorsal root ganglion (DRG) neurons, and there is a consequent increase in trafficking of α(2)δ-1 to their terminals. Furthermore, gabapentinoid drugs, which bind to α(2)δ-1 and α(2)δ-2, not only impair their trafficking, but also affect α(2)δ-1-dependent synaptogenesis. These drugs may interfere with α(2)δ function at several different levels.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Channels / biosynthesis
  • Calcium Channels / chemistry*
  • Calcium Channels / physiology*
  • Ganglia, Spinal / chemistry
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / pathology
  • Humans
  • Molecular Sequence Data
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / pathology
  • Presynaptic Terminals / physiology
  • Protein Transport / physiology
  • Sensory Receptor Cells / chemistry
  • Sensory Receptor Cells / pathology
  • Sensory Receptor Cells / physiology
  • Synaptic Transmission / physiology*
  • Up-Regulation / physiology


  • CACNA2D1 protein, human
  • Calcium Channels
  • voltage gated calcium channel subunit Ca alpha2delta-1, human