Functional role of the C-terminus of voltage-gated sodium channel Na(v)1.8.
Sodium channel Na(v)1.8 requires stronger depolarization than other sodium channels for activation and inactivation. The contribution of Na(v)1.8 C-terminus to this property was investigated by producing Na(v)1.8 and Na(v)1.4 chimeras and expressing them in ND7/23 cells. Current densities of the chimeras were significantly different than in parental channels, and the voltage-dependence of activation was depolarized in Na(v)1.4/1.8C compared to Na(v)1.4. Analysis of steady-state inactivation showed that only Na(v)1.8 and Na(v)1.4/1.8C currents demonstrate a non-inactivated fraction. Thus, the C-terminus of Na(v)1.8 contributes to regulation of channel density at the cell surface, modulates channel gating, and regulates the generation of sustained current.
Choi
Jin-Sung
JS
Department of Neurology, Yale University School of Medicine, New Haven CT 06510, USA.
Tyrrell
Lynda
L
Waxman
Stephen G
SG
Dib-Hajj
Sulayman D
SD
D002460:Cell Line; D005727:Ganglia, Spinal; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D062559:NAV1.8 Voltage-Gated Sodium Channel; D009474:Neurons / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D062559:NAV1.8 Voltage-Gated Sodium Channel; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C568317:SCN10A protein, human; D015222:Sodium Channels