Molecular basis of Ca(v)2.3 calcium channels in rat nociceptive neurons.
Ca(v)2.3 calcium channels play an important role in pain transmission in peripheral sensory neurons. Six Ca(v)2.3 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(v)2.3 isoforms unique to primary sensory neurons have not been identified. In this study, we determined Ca(v)2.3 isoforms expressed in the rat trigeminal ganglion neurons. Whole tissue reverse transcription (RT)-PCR analyses revealed that only two isoforms, Ca(v)2.3a and Ca(v)2.3e, are present in TG neurons. Using single cell RT-PCR, we found that Ca(v)2.3e is the major isoform, whereas Ca(v)2.3e expression is highly restricted to small (<16 mum) isolectin B4-negative and tyrosine kinase A-positive neurons. Ca(v)2.3e 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(v)2.3e expression. Our results suggest that Ca(v)2.3e in sensory neurons may be a potential target for the treatment of pain.
Fang
Zhi
Z
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Park
Chul-Kyu
CK
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Li
Hai Ying
HY
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Kim
Hyun Yeong
HY
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Park
Seong-Hae
SH
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Jung
Sung Jun
SJ
Department of Physiology, College of Medicine, Kangwon National University, Chunchon 200-710, Korea.
Kim
Joong Soo
JS
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea.
Monteil
Arnaud
A
Département de Physiologie, Institut de Génomique Fonctionnelle, CNRS-UMR 5203 141, Rue de la Cardonille 34396 Montpellier Cedex 5, France, and the.
Oh
Seog Bae
SB
Department of Physiology and Program in Molecular and Cellular Neuroscience, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 110-749, Korea. Electronic address: odolbae@snu.ac.kr.
Miller
Richard J
RJ
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611.
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D020908:Calcium Channels, R-Type / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D009475:Neurons, Afferent / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000235:genetics / Q000378:metabolism; D059408:Pain Management; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050916:TRPV Cation Channels / Q000096:biosynthesis; D012668:Trigeminal Ganglion / Q000378:metabolism*
D015415:Biomarkers; C498917:Cacna1e protein, rat; D020908:Calcium Channels, R-Type; D027682:Cation Transport Proteins; D020033:Protein Isoforms; D050916:TRPV Cation Channels; C494484:TRPV1 receptor