The role of changes in the extracellular potassium concentration [K+]o in epilepsy has remained unclear. Historically, it was hypothesized that [K+] o is the causal factor for epileptic seizures. This so-called potassium accumulation hypothesis led to substantial debate but subsequently failed to find wide acceptance. However, recent studies on the pathophysiology of tissue from epileptic human patients and animal epilepsy models revealed aberrations in [K+]o regulation. Computational models of cortical circuits that include ion concentration dynamics have catalyzed a renewed interest in the role of [K+]o in epilepsy. The authors here connect classical and more recent insights on [K+] o dynamics in the cortex with the goal of providing starting points for a next generation of [K+]o research. Such research may ultimately lead to an entirely new class of antiepileptic drugs that act on the [K+]o regulation system. NEUROSCIENTIST 14(5):422—433, 2008. DOI: 10.1177/1073858408317955
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