| First Author | Isaksen TJ | Year | 2017 |
| Journal | PLoS Genet | Volume | 13 |
| Issue | 5 | Pages | e1006763 |
| PubMed ID | 28472154 | Mgi Jnum | J:243291 |
| Mgi Id | MGI:5908060 | Doi | 10.1371/journal.pgen.1006763 |
| Citation | Isaksen TJ, et al. (2017) Hypothermia-induced dystonia and abnormal cerebellar activity in a mouse model with a single disease-mutation in the sodium-potassium pump. PLoS Genet 13(5):e1006763 |
| abstractText | Mutations in the neuron-specific alpha3 isoform of the Na+/K+-ATPase are found in patients suffering from Rapid onset Dystonia Parkinsonism and Alternating Hemiplegia of Childhood, two closely related movement disorders. We show that mice harboring a heterozygous hot spot disease mutation, D801Y (alpha3+/D801Y), suffer abrupt hypothermia-induced dystonia identified by electromyographic recordings. Single-neuron in vivo recordings in awake alpha3+/D801Y mice revealed irregular firing of Purkinje cells and their synaptic targets, the deep cerebellar nuclei neurons, which was further exacerbated during dystonia and evolved into abnormal high-frequency burst-like firing. Biophysically, we show that the D-to-Y mutation abolished pump-mediated Na+/K+ exchange, but allowed the pumps to bind Na+ and become phosphorylated. These findings implicate aberrant cerebellar activity in alpha3 isoform-related dystonia and add to the functional understanding of the scarce and severe mutations in the alpha3 isoform Na+/K+-ATPase. |
