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The Journal of Neurophysiology Vol. 81 No. 2 February 1999, pp. 413-424
Copyright ©1999 by the American Physiological Society
1Department of Anesthesia,
Electrophysiological evidence for tetrodotoxin-resistant sodium
channels in mechanosensitive nerve endings of slowly conducting fibers
in the intracranial dura. A tetrodotoxin (TTX)-resistant sodium channel was recently identified that is expressed only in small
diameter neurons of peripheral sensory ganglia. The peripheral axons of
sensory neurons appear to lack this channel, but its presence has not
been investigated in peripheral nerve endings, the site of sensory
transduction in vivo. We investigated the effect of TTX on
mechanoresponsiveness in nerve endings of sensory neurons that
innervate the intracranial dura. Because the degree of TTX resistance
of axonal branches could potentially be affected by factors other than
channel subtype, the neurons were also tested for sensitivity to
lidocaine, which blocks both TTX-sensitive and TTX-resistant sodium
channels. Single-unit activity was recorded from dural afferent neurons
in the trigeminal ganglion of urethan-anesthetized rats. Response
thresholds to mechanical stimulation of the dura were determined with
von Frey monofilaments while exposing the dura to progressively
increasing concentrations of TTX or lidocaine. Neurons with slowly
conducting axons were relatively resistant to TTX. Application of 1 µM TTX produced complete suppression of mechanoresponsiveness in all
(11/11) fast A-
units [conduction velocity (c.v.) 5-18 m/s] but
only 50% (5/10) of slow A-
units (1.5 <c.v.<5 m/s) and 13%
(2/15) of C units (c.v.
1.5 m/s). The mean TTX concentration that
produced complete suppression of mechanoresponsiveness was ~270-fold
higher in C units than in fast A-
units. In contrast, no significant
difference was found between C and A-
units in the concentration of
lidocaine required for complete suppression of mechanoresponsiveness,
indicating that the greater TTX resistance of mechanoresponsiveness in
C units is not attributable to differences in safety factor unrelated
to channel subtype. These data offer indirect evidence that a
TTX-resistant channel subtype is expressed in the terminal axonal
branches of many of the more slowly conducting (C and slow A-
) dural
afferents. The channel appears to be present in these fibers, but not
in the faster A-
fibers, in sufficient numbers to support the
initiation and propagation of mechanically induced impulses. Comparison
with previous data on the absence of TTX resistance in peripheral nerve
fibers suggests that the TTX-resistant sodium channel may be a
distinctive feature of the receptive rather than the conductive portion
of the sensory neuron's axonal membrane.
0022-3077/99
$5.00
Copyright © 1999 The American Physiological Society
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