Functional properties and oxidative modulation of A-type K+ currents in hippocampal granule cells of control and chronically epileptic rats.

Autor: Rüschenschmidt, C., Chen, J., Becker, A., Riazanski, V., Beck, H.
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Zdroj: European Journal of Neuroscience; Feb2006, Vol. 23 Issue 3, p675-685, 11p, 3 Charts, 5 Graphs
Abstrakt: A-type K+ channels are crucial determinants of neuronal firing. For example, reducing the amplitude of A-type currents ( IA) increases seizure susceptibility. We have therefore examined the functional and molecular properties of IA in dentate granule neurons following pilocarpine-induced status epilepticus (SE). We found that the levels of various A-type channel subunit mRNAs are unaltered following SE. Furthermore, current density and biophysical properties of IA recorded in outside-out and cell-attached patches from dentate granule cells are not modified by SE. However, IA in both control and epileptic rats was powerfully regulated by the cellular redox state. IA was recorded in outside-out patches with the recording pipette containing either reduced (GSH) or oxidized (GSSG) glutathione. In both control and epileptic rats, the presence of GSSG caused a similar, marked acceleration of recovery from inactivation. Additionally, GSSG produced a small but significant reduction of IA amplitudes only in control rats. The inactivation time course of IA during depolarizing voltage steps was not modified by GSH or GSSG. Cell-attached recordings, in which the intracellular milieu is conserved, revealed a slow time course of recovery more comparable to that with GSH. In summary, epileptic activity does not produce chronic changes in the molecular and functional properties of the somatic IA of dentate granule cells. However, IA is powerfully modulated by oxidation in both control and epileptic rats. This finding suggests that the availability of IA may be strongly regulated by changes in the GSH/GSSG ratio occurring during prolonged seizure activity or hypoxia. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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