Disturbance of membrane function preceding ischemic delayed neuronal death in the gerbil hippocampus.
Slice preparations were made from the hippocampus of gerbils after 5 min of ischemia by carotid artery occlusion and the membrane properties of pyramidal neurons were examined. A majority of CA1 neurons lost the capacity for long-term potentiation following tetanic stimulation of the input fibers. CA3 pyramidal neurons, in contrast, preserved responses similar to those in the normal gerbil. Following ischemia, CA1 pyramidal neurons showed increased spontaneous firing that was highly voltage dependent and was blocked by intracellular injection of the Ca2+ chelator, EGTA. Thirty-five percent of CA1 neurons showed an abnormal slow oscillation of the membrane potential after 24 h following ischemia. Intracellular injection of GTP gamma S or IP3 produced facilitation of the oscillations followed by irreversible depolarization. Our results indicate that ischemia-damaged CA1 neurons suffer from abnormal Ca2+ homeostasis, involving IP3-induced liberation of Ca2+ from internal stores.
Kirino
T
T
Department of Physiology, Jichi Medical School, Tochigi, Japan.
Robinson
H P
HP
Miwa
A
A
Tamura
A
A
Kawai
N
N
D000818:Animals; D002118:Calcium / Q000032:analysis*; D016923:Cell Death; D004195:Disease Models, Animal; D004533:Egtazic Acid / Q000494:pharmacology; D005849:Gerbillinae; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology*; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011712:Pyramidal Tracts / Q000503:physiopathology*; D015424:Reperfusion
D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium