A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons.
TTX-resistant (TTX-R) sodium currents are preferentially expressed in small C-type dorsal root ganglion (DRG) neurons, which include nociceptive neurons. Two mRNAs that are predicted to encode TTX-R sodium channels, SNS and NaN, are preferentially expressed in C-type DRG cells. To determine whether there are multiple TTX-R currents in these cells, we used patch-clamp recordings to study sodium currents in SNS-null mice and found a novel persistent voltage-dependent sodium current in small DRG neurons of both SNS-null and wild-type mice. Like SNS currents, this current is highly resistant to TTX (Ki = 39+/-9 microM). In contrast to SNS currents, the threshold for activation of this current is near 70 mV, the midpoint of steady-state inactivation is -44 +/- 1 mV, and the time constant for inactivation is 43+/-4 msec at 20 mV. The presence of this current in SNS-null and wild-type mice demonstrates that a distinct sodium channel isoform, which we suggest to be NaN, underlies this persistent TTX-R current. Importantly, the hyperpolarized voltage-dependence of this current, the substantial overlap of its activation and steady-state inactivation curves and its persistent nature suggest that this current is active near resting potential, where it may play an important role in regulating excitability of primary sensory neurons.
Cummins
T R
TR
Department of Neurology and PVA/EPVA Neuroscience Research Center, Yale Medical School, New Haven, Connecticut 06510, USA.
Dib-Hajj
S D
SD
Black
J A
JA
Akopian
A N
AN
Wood
J N
JN
Waxman
S G
SG
D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009475:Neurons, Afferent / Q000378:metabolism* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D015222:Sodium Channels; D013779:Tetrodotoxin