Dorsal root ganglion (DRG) neurons depend on nerve growth factor (NGF) for
survival during development, and for the maintenance of phenotypic expressi
on of neuropeptides in the adult. NGF also plays a role in the regulation o
f expression of functional sodium channels in both PC12 cells and DRG neuro
ns. Transgenic mice that overexpress NGF under the keratin promoter (hyper-
NGF mice) show increased levels of NGF in the skin from embryonic day 11 th
rough adulthood, hypertrophy of the peripheral nervous system and mechanica
l hyperalgesia, We show here that mRNA levels for specific sodium channel i
sotypes are greater in small (<30 mu m diameter) DRG neurons from hyper-NGF
mice compared to wild-type mice. Hybridization signals for sodium channel
subunits alpha II and beta 2 displayed the most substantial enhancement in
hyper-NGF mice, compared to wild-type mice DRG, and mRNA levels for alpha I
, NaG, Na6, SNS/PN3, NaN, and pr were also greater in hyper-NGF DRG, In con
trast, the levels of alpha II and PN1 mRNAs were similar in neurons from hy
per-NGF and wild-type DRG, Whole-cell patch-clamp studies showed no signifi
cant differences in the peak sodium current densities in hyper-NGF vs. wild
-type DRG neurons, These data demonstrate that DRG neurons in wild-type mic
e have a heterogeneous pattern of sodium channel expression, which is simil
ar to that previously described in rat, and suggest that transcripts of som
e, but not all, sodium channel mRNAs can be modulated by long-term overexpr
ession of NGF, (C) 1999 Wiley-Liss, Inc.