ATP1A3 dysfunction causes motor hyperexcitability and afterhyperpolarization loss in a dystonia model.

ABSTRACT: Mutations in the gene encoding the alpha3 Na+/K+-ATPase isoform (ATP1A3) lead to movement disorders that manifest with dystonia, a common neurological symptom with many different origins, but for which the underlying molecular mechanisms remain poorly understood. We have generated an ATP1A3 mutant mouse that displays motor impairments and a hyperexcitable motor phenotype compatible with dystonia. We show that neurons harbouring this mutation are compromised in their ability to extrude raised levels of intracellular sodium, highlighting a profound deficit in neuronal sodium homeostasis. We show that the spinal motor network in ATP1A3 mutant mice has a reduced responsiveness to activity-dependent rises in intracellular sodium and that this is accompanied by loss of the Na+/K+-ATPase-mediated

SUBMITTER: Akkuratov EE 

PROVIDER: S-EPMC11967811 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature