mTOR-dependent alterations of Kv1.1 subunit expression in the neuronal subset-specific Pten knockout mouse model of cortical dysplasia with epilepsy

Scientific Reports
Lena H Nguyen, Anne E Anderson

Abstract

Cortical dysplasia (CD) is a common cause for intractable epilepsy. Hyperactivation of the mechanistic target of rapamycin (mTOR) pathway has been implicated in CD; however, the mechanisms by which mTOR hyperactivation contribute to the epilepsy phenotype remain elusive. Here, we investigated whether constitutive mTOR hyperactivation in the hippocampus is associated with altered voltage-gated ion channel expression in the neuronal subset-specific Pten knockout (NS-Pten KO) mouse model of CD with epilepsy. We found that the protein levels of Kv1.1, but not Kv1.2, Kv1.4, or Kvβ2, potassium channel subunits were increased, along with altered Kv1.1 distribution, within the hippocampus of NS-Pten KO mice. The aberrant Kv1.1 protein levels were present in young adult (≥postnatal week 6) but not juvenile (≤postnatal week 4) NS-Pten KO mice. No changes in hippocampal Kv1.1 mRNA levels were found between NS-Pten KO and WT mice. Interestingly, mTOR inhibition with rapamycin treatment at early and late stages of the pathology normalized Kv1.1 protein levels in NS-Pten KO mice to WT levels. Together, these studies demonstrate altered Kv1.1 protein expression in association with mTOR hyperactivation in NS-Pten KO mice and suggest a role for...Continue Reading

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Citations

Feb 13, 2019·International Journal of Molecular Sciences·Shaip Krasniqi, Armond Daci
Aug 21, 2019·Cold Spring Harbor Perspectives in Medicine·Sebastian Rademacher, Britta J Eickholt
Apr 26, 2020·International Journal of Molecular Sciences·Maria Cristina D'AdamoPaola Imbrici
Oct 23, 2019·Journal of Molecular and Cellular Cardiology·Peter J KilfoilMatthew A Nystoriak
Feb 2, 2021·Frontiers in Neuroscience·Zhongshan ShiZao C Xu

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Methods Mentioned

BETA
PCR
protein assay
electrophoresis

Key Resources (RRID) Mentioned

MGI

Software Mentioned

Zeiss ZEN microscope
Prism
Image J
GraphPad

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