| Autor: |
Kohrman DC; Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109, USA., Smith MR, Goldin AL, Harris J, Meisler MH |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 1996 Oct 01; Vol. 16 (19), pp. 5993-9. |
| Abstrakt: |
The voltage-gated sodium channel Scn8a is broadly distributed in brain and spinal cord. We have identified a missense mutation in Scn8a that is associated with cerebellar ataxia in the jolting mutant, a mild allele of the "motor endplate disease" locus. The jolting mutation results in substitution of Thr for an evolutionarily conserved Ala residue in the cytoplasmic S4-S5 linker of domain III. Introduction of the corresponding mutation into the rat brain IIA sodium channel shifted the voltage dependence of activation by 14 mV in the depolarizing direction, without affecting the kinetics of fast inactivation or recovery from inactivation. A shift in the threshold of the Scn8a channel could account for the reduced spontaneous activity of Purkinje cells, reduced inhibitory output from the cerebellum, and loss of motor control observed in jolting mice. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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