Na⁺/K⁺-ATPase α isoform deficiency results in distinct spreading depolarization phenotypes.

ABSTRACT: Compromised Na⁺/K⁺-ATPase function is associated with the occurrence of spreading depolarization (SD). Mutations in ATP1A2, the gene encoding the α2 isoform of the Na⁺/K⁺-ATPase, were identified in patients with familial hemiplegic migraine type 2 (FHM2), a Mendelian model disease for SD. This suggests a distinct role for the α2 isoform in modulating SD susceptibility and raises questions about underlying mechanisms including the roles of other Na⁺/K⁺-ATPase α isoforms. Here, we investigated the effects of genetic ablation and pharmacological inhibition of α1, α2, and α3 on SD using heterozygous knock-out mice. We found that only α2 heterozygous mice displayed higher SD susceptibility when challenged with prolonged extracell

SUBMITTER: Reiffurth C 

PROVIDER: S-EPMC7025397 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature