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

Authors: Thomas J Bell, Christopher Thaler, Andrew J Castiglioni, Thomas D Helton, Diane Lipscombe

Journal, date & volume: Neuron, 2004 Jan 8 , 41, 127-38

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14715140

Abstract
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.