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.
Department of Neurology, Yale University School of Medicine, New Haven CT 06510, USA.
Jin-Sung
JS
Choi
Lynda
L
Tyrrell
Stephen G
SG
Waxman
Sulayman D
SD
Dib-Hajj
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