Molecular basis of Ca_v2.3 calcium channels in rat nociceptive neurons

Ca_v2.3 calcium channels play an important role in pain transmission in peripheral sensory neurons. Six Cav_v.3 isoforms resulting from different combinations of three inserts (inserts I and II in the II-III loop and insert III in the carboxyl-terminal region) have been identified in different mammalian tissues. To date, however, Ca_v2.3 isoforms unique to primary sensory neurons have not been identified. In this study, we determined Ca_v2.3 isoforms expressed in the rat trigeminal ganglion neurons. Whole tissue reverse transcription (RT)-PCR analyses revealed that only two isoforms, Ca_v2.3a and Ca_v2.3e, are present in TG neurons. Using single cell RT-PCR, we found that Ca_v2.3e is the major isoform, whereas Ca_v2.3e expression is highly restricted to small (<16 μm) isolectin B4-negative and tyrosine kinase A-positive neurons. Ca_v2.3e was also preferentially detected in neurons expressing the nociceptive marker, transient receptor potential vanilloid 1. Single cell RT-PCR following calcium imaging and whole-cell patch clamp recordings provided evidence of an association between an R-type calcium channel component and Ca_v2.3e expression. Our results suggest that Ca_v2.3e in sensory neurons may be a potential target for the treatment of pain.