Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice.
Sodium currents and action potentials were characterized in Purkinje neurons from ataxic mice lacking expression of the sodium channel Scn8a. Peak transient sodium current was approximately 60% of that in normal mice, but subthreshold sodium current was affected much more. Steady-state current elicited by voltage ramps was reduced to approximately 30%, and resurgent sodium current, an unusual transient current elicited on repolarization following strong depolarizations, was reduced to 8%-18%. In jolting mice, with a missense mutation in Scn8a, steady-state and resurgent current were also reduced, with altered voltage dependence and kinetics. Both spontaneous firing and evoked bursts of spikes were diminished in cells from null and jolting mice. Evidently Scn8a channels carry most subthreshold sodium current and are crucial for repetitive firing.
Raman
I M
IM
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sprunger
L K
LK
Meisler
M H
MH
Bean
B P
BP
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003433:Crosses, Genetic; D005071:Evoked Potentials / Q000187:drug effects; D005838:Genotype; D006579:Heterozygote; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011689:Purkinje Cells / Q000502:physiology*; D015222:Sodium Channels / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology*; D013997:Time Factors
D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D002118:Calcium