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The Journal of Neuroscience, October 15, 2001, 21(20):7909-7918
Gating Properties of Nav1.7 and Nav1.8
Peripheral Nerve Sodium Channels
Kausalia
Vijayaragavan1, 2,
Michael E.
O'Leary3, and
Mohamed
Chahine1, 2
1 Laval University, Faculty of Medicine, Sainte-Foy,
Québec, Canada G1K 7P4, 2 Québec Heart
Institute, Laval Hospital, Research Center, Sainte-Foy, Québec,
Canada G1V 4G5, and 3 Department of Pathology, Anatomy and
Cell Biology, Thomas Jefferson Medical College, Philadelphia,
Pennsylvania 19107
Several distinct components of voltage-gated sodium current have
been recorded from native dorsal root ganglion (DRG) neurons that
display differences in gating and pharmacology. This study compares the
electrophysiological properties of two peripheral nerve sodium channels
that are expressed selectively in DRG neurons (Nav1.7 and Nav1.8). Recombinant
Nav1.7 and Nav1.8 sodium channels were
coexpressed with the auxiliary 1 subunit in
Xenopus oocytes. In this system coexpression of the
1 subunit with Nav1.7 and Nav1.8
channels results in more rapid inactivation, a shift in midpoints of
steady-state activation and inactivation to more hyperpolarizing
potentials, and an acceleration of recovery from inactivation. The
coinjection of 1 subunit also significantly increases
the expression of Nav1.8 by sixfold but has no effect on
the expression of Nav1.7. In addition, a great percentage
of Nav1.8+ 1 channels is observed to enter
rapidly into the slow inactivated states, in contrast to
Nav1.7+ 1 channels. Consequently, the rapid entry into
slow inactivation is believed to cause a frequency-dependent reduction
of Nav1.8+ 1 channel amplitudes, seen during
repetitive pulsing between 1 and 2 Hz. However, at higher frequencies
(>20 Hz) Nav1.8+ 1 channels reach a steady state to ~42% of total current. The presence of this steady-state sodium channel activity, coupled with the high activation threshold (V0.5 = 3.3 mV) of
Nav1.8+ 1, could enable the
nociceptive fibers to fire spontaneously after nerve injury.
Key words:
Nav1.7; Nav1.8; peripheral nerve
sodium channels; expression; dorsal root ganglion; nociception; Xenopus oocytes
Copyright © 2001 Society for Neuroscience 0270-6474/01/21207909-10$05.00/0
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