Functional analysis of the mouse Scn8a sodium channel.
The mouse Scn8a sodium channel and its ortholog Na6 in the rat are abundantly expressed in the CNS. Mutations in mouse Scn8a result in neurological disorders, including paralysis, ataxia, and dystonia. In addition, Scn8a has been observed to mediate unique persistent and resurgent currents in cerebellar Purkinje cells (Raman et al., 1997). To examine the functional characteristics of this channel, we constructed a full-length cDNA clone encoding the mouse Scn8a sodium channel and expressed it in Xenopus oocytes. The electrophysiological properties of the Scn8a channels were compared with those of the Rat1 and Rat2 sodium channels. Scn8a channels were sensitive to tetrodotoxin at a level comparable to that of Rat1 or Rat2. Scn8a channels inactivated more rapidly and showed differences in their voltage-dependent properties compared with Rat1 and Rat2 when only the alpha subunits were expressed. Coexpression of the beta1 and beta2 subunits modulated the properties of Scn8a channels, but to a lesser extent than for the Rat1 or Rat2 channels. Therefore, all three channels showed similar voltage dependence and inactivation kinetics in the presence of the beta subunits. Scn8a channels coexpressed with the beta subunits exhibited a persistent current that became larger with increasing depolarization, which was not observed for either Rat1 or Rat2 channels. The unique persistent current observed for Scn8a channels is consistent with the hypothesis that this channel is responsible for distinct sodium conductances underlying repetitive firing of action potentials in Purkinje neurons.
Department of Microbiology and Molecular Genetics and Physiology and Biophysics, University of California, Irvine, California 92697-4025, USA.
M R
MR
Smith
R D
RD
Smith
N W
NW
Plummer
M H
MH
Meisler
A L
AL
Goldin
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004553:Electric Conductivity; D005095:Exoribonucleases / Q000502:physiology; D005260:Female; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis
D018076:DNA, Complementary; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D005095:Exoribonucleases