Transcriptomic changes triggered by ouabain in rat cerebellum granule cells: Role of ?3- and ?1-Na+,K+-ATPase-mediated signaling.

ABSTRACT: It was shown previously that inhibition of the ubiquitous ?1 isoform of Na+,K+-ATPase by ouabain sharply affects gene expression profile via elevation of intracellular [Na+]i/[K+]i ratio. Unlike other cells, neurons are abundant in the ?3 isoform of Na+,K+-ATPase, whose affinity in rodents to ouabain is 104-fold higher compared to the ?1 isoform. With these sharp differences in mind, we compared transcriptomic changes in rat cerebellum granule cells triggered by inhibition of ?1- and ?3-Na+,K+-ATPase isoforms. Inhibition of ?1- and ?3-Na+,K+-ATPase isoforms by 1 mM ouabain resulted in dissipation of transmembrane Na+ and K+ gradients and differential expression of 994 transcripts, whereas selective inhibition of ?3-Na+,K+-ATPase isoform by 100 nM ouabain affected expression of 144 transcripts without any impact on the [Na+]i/[K+]i ratio. The list of genes whose expression was affected by 1 mM ouabain by more than 2-fold was abundant in intermediates of intracellular signaling and transcription regulators, including augmented content of Npas4, Fos, Junb, Atf3, and Klf4 mRNAs, whose upregulated expression was demonstrated in neurons subjected to electrical and glutamatergic stimulation. The role [Na+]i/[K+]i-mediated signaling in transcriptomic changes involved in memory formation and storage should be examined further.

SUBMITTER: Smolyaninova LV 

PROVIDER: S-EPMC6762055 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature