Cell-specific alternative splicing increases calcium channel current density in the pain pathway

Neuron. 2004 Jan 8;41(1):127-38. doi: 10.1016/s0896-6273(03)00801-8.


N-type calcium channels are critical for pain transduction. Inhibitors of these channels are powerful analgesics, but clinical use of current N-type blockers remains limited by undesirable actions in other regions of the nervous system. We now demonstrate that a unique splice isoform of the N-type channel is restricted exclusively to dorsal root ganglia. By a combination of functional and molecular analyses at the single-cell level, we show that the DRG-specific exon, e37a, is preferentially present in Ca(V)2.2 mRNAs expressed in neurons that contain nociceptive markers, VR1 and Na(V)1.8. Cell-specific inclusion of exon 37a correlates closely with significantly larger N-type currents in nociceptive neurons. This unique splice isoform of the N-type channel could represent a novel target for pain management.

Publication types

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

MeSH terms

  • Alternative Splicing*
  • Animals
  • Calcium Channels, L-Type / genetics*
  • Calcium Channels, L-Type / metabolism*
  • Calcium Channels, N-Type / metabolism
  • Capsaicin / pharmacology
  • Electric Conductivity
  • Exons
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Nociceptors / drug effects
  • Nociceptors / metabolism
  • Pain / genetics
  • Pain / physiopathology*
  • Protein Isoforms / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Cacna1b protein, rat
  • Calcium Channels, L-Type
  • Calcium Channels, N-Type
  • Protein Isoforms
  • Capsaicin