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The Journal of Neuroscience, August 15, 1998, 18(16):6093-6102

Functional Analysis of the Mouse Scn8a Sodium Channel

Marianne R. Smith¹, Raymond D. Smith¹, Nicholas W. Plummer², Miriam H. Meisler², and Alan L. Goldin¹

¹ Department of Microbiology and Molecular Genetics and Physiology and Biophysics, University of California, Irvine, California 92697-4025, and ² Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109-0618

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 (). 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  subunits were expressed. Coexpression of the ₁ and ₂ 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  subunits. Scn8a channels coexpressed with the  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.

Key words: sodium channel; cloning; expression; Xenopus oocytes; brain; RT-PCR; Purkinje cells; resurgent current; persistent current

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18166093-10$05.00/0

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