title: Gating properties of Na(v)1.7 and Na(v)1.8 peripheral nerve sodium channels.
abstract: 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 (Na(v)1.7 and Na(v)1.8). Recombinant Na(v)1.7 and Na(v)1.8 sodium channels were coexpressed with the auxiliary beta(1) subunit in Xenopus oocytes. In this system coexpression of the beta(1) subunit with Na(v)1.7 and Na(v)1.8 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 beta(1) subunit also significantly increases the expression of Na(v)1.8 by sixfold but has no effect on the expression of Na(v)1.7. In addition, a great percentage of Na(v)1.8+beta(1) channels is observed to enter rapidly into the slow inactivated states, in contrast to Nav1.7+beta(1) channels. Consequently, the rapid entry into slow inactivation is believed to cause a frequency-dependent reduction of Na(v)1.8+beta(1) channel amplitudes, seen during repetitive pulsing between 1 and 2 Hz. However, at higher frequencies (>20 Hz) Na(v)1.8+beta(1) channels reach a steady state to approximately 42% of total current. The presence of this steady-state sodium channel activity, coupled with the high activation threshold (V(0.5) = -3.3 mV) of Na(v)1.8+beta(1), could enable the nociceptive fibers to fire spontaneously after nerve injury.
authors.affiliation: Laval University, Faculty of Medicine, Sainte-Foy, Québec, Canada G1K 7P4.
authors.forename: K
authors.initials: K
authors.lastname: Vijayaragavan
authors.forename: M E
authors.initials: ME
authors.lastname: O'Leary
authors.forename: M
authors.initials: M
authors.lastname: Chahine
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005727:Ganglia, Spinal / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010525:Peripheral Nerves / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
chemical_list: D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; D011994:Recombinant Proteins; D026941:Sodium Channel Blockers; D015222:Sodium Channels