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

• DOI: 10.3390/brainsci10020072
• Publication Date: 2020-02-03T06:25:51Z
• Authors: Miguel P. Méndez-...; David E. Rivera-A...; Jan Benedikt; Geronimo Maldonad...; Flavia Tejeda-Bayron; Serguei N. Skatchkov; Misty J. Eaton
• Keywords: Pyramidal cell; Premovement neuronal activity; Population spike

Epilepsy, characterized by recurrent seizures, affects 1% of the general population. Interestingly, 25% diabetics develop seizures with a yet unknown mechanism. Hyperglycemia downregulates inwardly rectifying potassium channel 4.1 (Kir4.1) in cultured astrocytes. Therefore, present study aims to determine if downregulation functional astrocytic Kir4.1 channels occurs brains type 2 diabetic mice and could influence hippocampal neuronal hyperexcitability. Using whole-cell patch clamp recording brain slices from male mice, we determined electrophysiological properties stratum radiatum astrocytes CA1 pyramidal neurons. In were functionally downregulated as evidenced multiple characteristics including depolarized membrane potential, reduced barium-sensitive Kir currents impaired uptake capabilities Furthermore, neurons displayed increased spontaneous activity: action potential frequency was ≈9 times higher compared non-diabetic small EPSC event significantly cells non-diabetics. These differences apparent control conditions largely pronounced response pro-convulsant 4-aminopyridine. Our data suggest that dysfunction due may increase seizure susceptibility impairing ability maintain proper extracellular homeostasis.