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Open AccessArticle

Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice

1
Department of Biochemistry, Universidad Central del Caribe, Bayamón, PR 00960-6032, USA
2
Department of Sciences and Technology, Antilles Adventist University, Mayaguez, PR 00680, USA
3
Department of Natural Sciences, University of Puerto Rico, Aguadilla, PR 00604-6150, USA
4
Departments of Physiology and Biochemistry Universidad Central del Caribe, Bayamón, PR 00960-6032, USA
5
School of Chiropractic, Universidad Central del Caribe, Bayamón, PR 00960-6032, USA
*
Authors to whom correspondence should be addressed.
Brain Sci. 2020, 10(2), 72; https://doi.org/10.3390/brainsci10020072
Received: 10 January 2020 / Accepted: 22 January 2020 / Published: 30 January 2020
(This article belongs to the Special Issue Synaptic Changes in Epilepsy)
Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% of diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, the present study aims to determine if downregulation of functional astrocytic Kir4.1 channels occurs in brains of type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording in hippocampal brain slices from male mice, we determined the electrophysiological properties of stratum radiatum astrocytes and CA1 pyramidal neurons. In diabetic mice, astrocytic Kir4.1 channels were functionally downregulated as evidenced by multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents and impaired potassium uptake capabilities of hippocampal astrocytes. Furthermore, CA1 pyramidal neurons from diabetic mice displayed increased spontaneous activity: action potential frequency was ≈9 times higher in diabetic compared with non-diabetic mice and small EPSC event frequency was significantly higher in CA1 pyramidal cells of diabetics compared to non-diabetics. These differences were apparent in control conditions and largely pronounced in response to the pro-convulsant 4-aminopyridine. Our data suggest that astrocytic dysfunction due to downregulation of Kir4.1 channels may increase seizure susceptibility by impairing astrocytic ability to maintain proper extracellular homeostasis. View Full-Text
Keywords: diabetes; hyperexcitability; astrocytes; Kir4.1; hippocampus; potassium uptake diabetes; hyperexcitability; astrocytes; Kir4.1; hippocampus; potassium uptake
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Méndez-González, M.P.; Rivera-Aponte, D.E.; Benedikt, J.; Maldonado-Martínez, G.; Tejeda-Bayron, F.; Skatchkov, S.N.; Eaton, M.J. Downregulation of Astrocytic Kir4.1 Potassium Channels Is Associated with Hippocampal Neuronal Hyperexcitability in Type 2 Diabetic Mice. Brain Sci. 2020, 10, 72.

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