Selective inhibition of inositol 1,4,5-triphosphate-induced Ca2+ release in the CA1 region of the hippocampus in the ischemic gerbil.
We examined the effect of ischemia on inositol 1,4,5-trisphosphate receptor-induced Ca2+ release by functional and morphological approaches, using the gerbil model after 6-h unilateral occlusion of the common carotid artery. Autoradiographic study revealed that the basal uptake of 45Ca2+ into the endoplasmic reticulum and caffeine-induced 45Ca2+ release from the endoplasmic reticulum were normal in the presence of ATP in each ischemic brain region, whereas inositol 1,4,5-trisphosphate receptor-induced 45Ca2+ release from the endoplasmic reticulum was inhibited only in the CA1 region of the hippocampus on the ischemic side. In moderately ischemic gerbils, electron microscopic study demonstrated aggregation of swollen endoplasmic reticulum in the CA1 region of the hippocampus, so that abundant endoplasmic reticulum assembled in close contact to form endoplasmic reticulum cisternal stacks. In severely ischemic gerbils, immunohistochemical analysis of the hippocampus showed loss of type 1 inositol 1,4,5-trisphosphate receptor protein with preservation of immunoreactivity for type 2 and 3 inositol 1,4,5-trisphosphate receptor proteins, which was confirmed by western blot analysis. Such selective inhibition of inositol 1,4,5-trisphosphate receptor-induced Ca2+ release and the loss of type 1 inositol 1,4,5-trisphosphate receptor in the CA1 region of the hippocampus in cerebral ischemia may be associated with its region-specific vulnerability to ischemia.
Nagata
E
E
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Tanaka
K
K
Suzuki
S
S
Dembo
T
T
Fukuuchi
Y
Y
Futatsugi
A
A
Mikoshiba
K
K
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D017536:Carotid Artery, Common; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003250:Constriction; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate