Neuron
Volume 41, Issue 1, 8 January 2004, Pages 127-138
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Article
Cell-Specific Alternative Splicing Increases Calcium Channel Current Density in the Pain Pathway

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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 CaV2.2 mRNAs expressed in neurons that contain nociceptive markers, VR1 and NaV1.8. 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.

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Present address: Laboratory of Molecular Physiology, Section on Cellular Biophotonics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Flow Building, Room 15, 12501 Washington Avenue, Rockville, Maryland 20852.