Modulation of Voltage-Gated Ca^<2+> Current by 4-Hydroxynonenal in Dentate Granule Cells(Highlighted paper setected by Editor-in-cfiief)(Pharmacology)

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Although recent studies have suggested that dentate granule cells play a key role in hippocampal functions, electrophysiological properties in these cells have not been sufficiently explored. In the present study, modification of voltage-gated Ca^<2+> channels by 4-hydroxynonenal (4HN), a major aldehydic product of membrane lipid peroxidation, in cultured dentate granule cells was examined using the whole-cell patch clamp technique. When whole-cell voltage clamp was applied, the cells exhibited a high-voltage-activated Ca^<2+> current, which was totally sensitive to 30 μM Ca^<2+> and partially sensitive to 2 μM nifedipine. 4HN enhanced the Ca^<2+> current in these cells. When L-type Ca^<2+> channels were blocked by application of nifedipine, the enhancement was completely canceled, whereas application of ω-conotoxin-GVIA or ω-agatoxin-IVA, blockers of N- and P/Q-type Ca^<2+> channels, respectively, had no effect. These results suggest that 4HN modulates L-type Ca^<2+> channels in the dentate granule cells, and thereby plays a role in the physiological and pathophysiological responses of these cells to oxidative stress.
社団法人日本薬学会の論文
2004-02-01