Tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunit subtypes

J Membr Biol. 2001 Nov 1;184(1):35-43. doi: 10.1007/s00232-001-0072-7.


We report here the tissue-specific expression and gabapentin-binding properties of calcium channel alpha2delta subunits. Northern blot analysis demonstrated that human alpha2delta-1, -2, and -3 mRNA all had high levels of expression in brain, heart and skeletal muscle. However, the highest expression of human alpha2delta-2 mRNA was found in lung. Human alpha2delta-1, -2, and -3 mRNAs were detected in all portions of brain tested. Western blotting revealed that alpha2delta-2 protein was predominantly expressed in cerebellar cortex (brain) and undetectable in lung. The dissociation between mRNA and protein levels of human alpha2delta-2 in lung suggests possible post-transcriptional regulation. Although mouse alpha2delta-1 proteins exhibited a similar tissue distribution profile as that of human, tissue distribution of mouse alpha2delta-2 and -3 mRNA revealed a different profile. Mouse alpha2delta-3 mRNA was restricted to brain and mouse alpha2delta-2 mRNA was not detectable in lung. Gel electrophoresis under a reduced condition resulted in a mobility shift of both alpha2delta-1 and alpha2delta-2 proteins, suggesting that alpha2 and delta of alpha2delta-2 protein are linked by disulfide bond as are alpha2 and delta of alpha2delta-1. Scatchard plots revealed a single population of gabapentin binding sites for human alpha2delta-2 with the KD value twofold higher than that of porcine alpha2delta-1 (156 +/- 25 nm vs. 72 +/- 9 nm). Inhibition of gabapentin binding to alpha2delta-2 by selected amino acids and gabapentin analogs produced a binding profile similar, but not identical to that of alpha2delta-1.

MeSH terms

  • Acetates / metabolism*
  • Amines*
  • Amino Acids / metabolism
  • Animals
  • Anticonvulsants / metabolism
  • Binding Sites
  • Calcium Channels / chemistry
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Line
  • Cyclohexanecarboxylic Acids*
  • Gabapentin
  • Humans
  • Mice
  • Protein Binding
  • Protein Isoforms
  • Protein Structure, Secondary
  • Protein Subunits
  • Radioligand Assay
  • Tissue Distribution
  • gamma-Aminobutyric Acid*


  • Acetates
  • Amines
  • Amino Acids
  • Anticonvulsants
  • Calcium Channels
  • Cyclohexanecarboxylic Acids
  • Protein Isoforms
  • Protein Subunits
  • gamma-Aminobutyric Acid
  • Gabapentin