Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling.
Astrocytes are endowed with the machinery to sense and respond to neuronal activity. Recent work has demonstrated that astrocytes play important physiological roles in the CNS, e.g., they synchronize action potential firing, ensure ion homeostasis, transmitter clearance and glucose metabolism, and regulate the vascular tone. Astrocytes are abundantly coupled through gap junctions, which is a prerequisite to redistribute elevated K(+) from sites of excessive neuronal activity to sites of lower extracellular K(+) concentration. Recent studies identified dysfunctional astrocytes as crucial players in epilepsy. Investigation of specimens from patients with pharmacoresistant temporal lobe epilepsy and epilepsy models revealed alterations in expression, localization, and function of astroglial inwardly rectifying K(+) (Kir) channels, particularly Kir4.1, which is suspected to entail impaired K(+) buffering. Gap junctions in astrocytes appear to play a dual role: on the one hand they counteract the generation of hyperactivity by facilitating clearance of elevated extracellular K(+) levels while in contrast, they constitute a pathway for energetic substrate delivery to fuel neuronal (hyper)activity. Recent work suggests that astrocyte dysfunction is causative of the generation or spread of seizure activity. Thus, astrocytes should be considered as promising targets for alternative antiepileptic therapies.
Institute of Cellular Neurosciences, University of Bonn, Bonn, Germany. christian.steinhaeuser@ukb.uni-bonn.de
Christian
C
Steinhäuser
Gerald
G
Seifert
Peter
P
Bedner
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000473:pathology*; D017629:Gap Junctions / Q000502:physiology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*
D017630:Connexins; D015221:Potassium Channels