Sodium channel expression in NGF-overexpressing transgenic mice.
Dorsal root ganglion (DRG) neurons depend on nerve growth factor (NGF) for survival during development, and for the maintenance of phenotypic expression of neuropeptides in the adult. NGF also plays a role in the regulation of expression of functional sodium channels in both PC12 cells and DRG neurons. Transgenic mice that overexpress NGF under the keratin promoter (hyper-NGF mice) show increased levels of NGF in the skin from embryonic day 11 through adulthood, hypertrophy of the peripheral nervous system and mechanical hyperalgesia. We show here that mRNA levels for specific sodium channel isotypes are greater in small (< 30 microm diameter) DRG neurons from hyper-NGF mice compared to wild-type mice. Hybridization signals for sodium channel subunits alphaII and beta2 displayed the most substantial enhancement in hyper-NGF mice, compared to wild-type mice DRG, and mRNA levels for alphaI, NaG, Na6, SNS/PN3, NaN, and beta1 were also greater in hyper-NGF DRG. In contrast, the levels of alphaII and PN1 mRNAs were similar in neurons from hyper-NGF and wild-type DRG. Whole-cell patch-clamp studies showed no significant differences in the peak sodium current densities in hyper-NGF vs. wild-type DRG neurons. These data demonstrate that DRG neurons in wild-type mice have a heterogeneous pattern of sodium channel expression, which is similar to that previously described in rat, and suggest that transcripts of some, but not all, sodium channel mRNAs can be modulated by long-term overexpression of NGF.
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
J
J
Fjell
T R
TR
Cummins
B M
BM
Davis
K M
KM
Albers
K
K
Fried
S G
SG
Waxman
J A
JA
Black
D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D015222:Sodium Channels / Q000096:biosynthesis* / Q000502:physiology
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015222:Sodium Channels