Sodium-calcium exchanger and multiple sodium channel isoforms in intra-epidermal nerve terminals.
BACKGROUND
Nociception requires transduction and impulse electrogenesis in nerve fibers which innervate the body surface, including the skin. However, the molecular substrates for transduction and action potential initiation in nociceptors are incompletely understood. In this study, we examined the expression and distribution of Na+/Ca2+ exchanger (NCX) and voltage-gated sodium channel isoforms in intra-epidermal free nerve terminals.


RESULTS
Small diameter DRG neurons exhibited robust NCX2, but not NCX1 or NCX3 immunolabeling, and virtually all PGP 9.5-positive intra-epidermal free nerve terminals displayed NCX2 immunoreactivity. Sodium channel NaV1.1 was not detectable in free nerve endings. In contrast, the majority of nerve terminals displayed detectable levels of expression of NaV1.6, NaV1.7, NaV1.8 and NaV1.9. Sodium channel immunoreactivity in the free nerve endings extended from the dermal boundary to the terminal tip. A similar pattern of NCX and sodium channel immunolabeling was observed in DRG neurons in vitro.


CONCLUSIONS
NCX2, as well as NaV1.6, NaV1.7, NaV1.8 and NaV1.9, are present in most intra-epidermal free nerve endings. The presence of NCX2, together with multiple sodium channel isoforms, in free nerve endings may have important functional implications.
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT 06510, USA.
Anna-Karin
AK
Persson
Joel A
JA
Black
Andreas
A
Gasser
Xiaoyang
X
Cheng
Tanya Z
TZ
Fischer
Stephen G
SG
Waxman
D000818:Animals; D004817:Epidermis / Q000294:innervation*; D007150:Immunohistochemistry; D008297:Male; D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009411:Nerve Endings / Q000737:chemistry*; D009479:Neuropeptides; D009619:Nociceptors; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000032:analysis*; D019831:Sodium-Calcium Exchanger / Q000032:analysis*
D062556:NAV1.7 Voltage-Gated Sodium Channel; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009479:Neuropeptides; D020033:Protein Isoforms; C568319:Scn10a protein, rat; C113705:Scn11a protein, rat; C503480:Scn9a protein, rat; C110927:Slc8a2 protein, rat; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger