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The Antiepileptic Effect of the Glycolytic Inhibitor 2-Deoxy-d-Glucose is Mediated by Upregulation of KATP Channel Subunits Kir6.1 and Kir6.2

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Abstract

Metabolic modulation of neuronal excitability is becoming increasingly important as an antiepileptic therapy. It was reported that the glycolytic inhibitor 2-deoxy-d-glucose (2-DG) and the activation of the ATP-sensitive potassium ion channel (KATP channel) had an antiepileptic effect in models of epilepsy. To explore whether 2-DG exerts an antiepileptic effect through upregulation of the KATP channel subunits Kir6.1 and Kir6.2, the expression of these subunits in hippocampus of five groups of mice with pilocarpine-induced status epilepticus (SE) was evaluated. A seizure group with pilocarpine-kindling convulsions (EP) was compared to similar groups treated with high, medium, and low 2-DG concentrations (100–500 mg/kg) and a normal control group (Con). Kir6.1 and Kir6.2 mRNAs and proteins were analyzed at 4 h, 1 days (acute period), 7 days (latent period), 30, and 60 days (chronic period) following SE. In the seizure group (compared to the Con group), hippocampal expression of Kir6.1 and Kir6.2 increased dramatically at 1, 7, and 30 days, and was further increased after treatment with medium and high dose 2-DG (all P < 0.05). Our results suggest that 2-DG may exert an antiepileptic effect through up-regulation of mRNAs and protein levels of Kir6.1 and Kir6.2, which may therefore be used as molecular targets in the treatment of epilepsy with 2-DG.

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Acknowledgments

This work was supported by the NFSC 30971534 and 125 Projects of the Third Xiangya Hospital. The funding agency had no role in study design, data collection, analysis, interpretation of data, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors declare that research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We confirm that we have read the Journal’s position on the issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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Authors and Affiliations

  1. Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People’s Republic of China

    Heng Yang, Ren Guo, Jiongxing Wu, Yufeng Peng, Dujie Xie, Wen Zheng, Xian Huang, Ding Liu, Wei Liu, Lihua Huang & Zhi Song

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  1. Heng Yang
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Correspondence to Zhi Song.

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Yang, H., Guo, R., Wu, J. et al. The Antiepileptic Effect of the Glycolytic Inhibitor 2-Deoxy-d-Glucose is Mediated by Upregulation of KATP Channel Subunits Kir6.1 and Kir6.2. Neurochem Res 38, 677–685 (2013). https://doi.org/10.1007/s11064-012-0958-z

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