A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting
DC Kohrman, MR Smith, AL Goldin… - Journal of …, 1996 - Soc Neuroscience
DC Kohrman, MR Smith, AL Goldin, J Harris, MH Meisler
Journal of Neuroscience, 1996•Soc NeuroscienceThe 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 …
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 …
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 joltingmutant, a mild allele of the “motor endplate disease” locus. Thejolting 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 injolting mice.
Soc Neuroscience