Modulation of Voltage-Gated Ca²⁺ Current by 4-Hydroxynonenal in Dentate Granule Cells

抄録

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 Ca²⁺ 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 Ca²⁺ current, which was totally sensitive to 30 μM Cd²⁺ and partially sensitive to 2 μM nifedipine. 4HN enhanced the Ca²⁺ current in these cells. When L-type Ca²⁺ 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 Ca²⁺ channels, respectively, had no effect. These results suggest that 4HN modulates L-type Ca²⁺ channels in the dentate granule cells, and thereby plays a role in the physiological and pathophysiological responses of these cells to oxidative stress.