| 17604346 |
Andreasen M, Skov J, Nedergaard S: Inwardly rectifying K (+) (Kir) channels antagonize ictal-like epileptiform activity in area CA1 of the rat hippocampus. Hippocampus. 2007;17(11):1037-48.
Reactive glial cells, for example, from patients with temporal lope epilepsy have a reduced density of inward rectifying K (+) (Kir) channels and thus a reduced K (+) buffering capacity. Evidence is accumulating that this downregulation of Kir channels could be implicated in epileptogenesis. In rat hippocampal brain slices, prolonged exposure to the nonselective Kir channel antagonist, Cs (+) (5 mM), gives rise to an epileptiform field potential (Cs-FP) in area CA1 composed of an initial positive (interictal-like) phase followed by a prolonged negative (ictal-like) phase. We have previously shown that the interictal-like phase depends on synaptic activation. The present study extends these findings by showing that the ictal-like phase of the Cs-FP is (i) sensitive to osmotic expansion of the extracellular space, (ii) reversed very quickly during wash out of Cs (+), and (iii) re-established in the presence of Ba (2+) (30-200 microM) or isosmotic low extracellular concentration of Na (+) ([Na (+)](o), 51.25 mM). The interictal-like phase showed less or no sensitivity to these treatments. In the complete absence of Cs (+), the Cs-FP could be fully reconstructed by the combined application of 4-aminopyridine (0.5 mM), an isosmotic high extracellular concentration of K (+) ([K (+)](o), 7 mM), and low [Na (+)](o) (51.25 mM). These results suggest that the interictal-like phase is initiated through synaptic activation and results from an unspecific increase in neuronal excitability, whereas the ictal-like phase is entirely dependent on blockade of Kir channels in CA1. We propose that glial dysfunction-related loss of Kir channels may not alone be sufficient for starting the induction process, but will likely increase the tendency of an epileptogenic process to proceed into seizure activity. |
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