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

Accession number;04A0108789
Title;Modulation of Voltage-Gated Ca2+ Current by 4-Hydroxynonenal in Dentate Granule Cells
Author; AKAISHI T (Nihon Univ. Funabashi, Jpn) NAKAZAWA K (National Inst. Health Sci., Tokyo, Jpn) SATO K (National Inst. Health Sci., Tokyo, Jpn) SAITO H (Nihon Univ. Funabashi, Jpn) OHNO Y (National Inst. Health Sci., Tokyo, Jpn) ITO Y (Nihon Univ. Funabashi, Jpn)
Journal Title;Biol Pharm Bull
Journal Code:S0989A
ISSN:0918-6158
VOL.27;NO.2;PAGE.174-179(2004)
Figure&Table&Reference;FIG.5, REF.40
Pub. Country;Japan
Language;English
Abstract;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 .MU.M Cd2+ and partially sensitive to 2 .MU.M 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 .OMEGA.-conotoxin-GVIA or .OMEGA.-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. (author abst.)
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