Aberrant Potassium Handling by Astrocytes and Epileptic Seizures: A Synthetic Update

Excessive extracellular accumulation of K + plays a key role in the induction and propagation of seizures associated with temporal lobe epilepsy (TLE), and astrocytes are largely responsible for K + clearance from the extracellular space. Here, we review the TLE‐related changes in the content and/or activity of proteins contributing to K + transport across the astrocytic cell membranes. Seizures, whether genetic or acquired, are linked with decreased expression and/or mislocalization of the two key astroglia‐specific drivers of K + uptake: the inward rectifying potassium channel K ir 4.1 and its spatial and functional partner, the water channel aquaporin 4 (AQP4). Among neural cells of the CNS, the high K + ‐responsive α2 isoform of Na + /K + ‐ATPase is specific for astrocytes and is substantially inactivated in the brains of TLE patients and experimental animals, albeit not always in epilepsies with a genetic background. The above data consistently support the involvement of malfunctional astrocytic K + transport as a factor facilitating seizures. By contrast, complex and variable, region‐dependent dynamics of the two‐pore domain potassium channels (K2P; TWIK, TASK, and TREK) were observed in astrocytes in the hippocampus, rendering their contribution to seizures difficult to interpret. Anti‐seizure medication targeting metabolic processes not directly related to astrocytic K + transport often reversed the unfavorably changed status of the astrocytic mediators of K + buffering.