Modulation of voltage-gated Ca2+ current by 4-hydroxynonenal in dentate granule cells.
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 microM Cd2+ and partially sensitive to 2 microM 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.
Akaishi
Tatsuhiro
T
Department of Pharmacology, College of Pharmacy, Nihon University, Funabashi 274-8555, Japan.
Nakazawa
Ken
K
Sato
Kaoru
K
Saito
Hiroshi
H
Ohno
Yasuo
Y
Ito
Yoshihisa
Y
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D015640:Ion Channel Gating; D009543:Nifedipine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000447:Aldehydes; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; C027576:4-hydroxy-2-nonenal