Elevated cytosolic calcium in cerebrocortical nerve terminals of rats during prolonged ethanol ingestion.
Increases in cytosolic free calcium concentrations ([Ca++]i) may underlie acute neuronal degeneration during ischemic or anoxic episodes, seizures and excitotoxin treatment. With quin-2 and fura-2 fluorescent probes, we have obtained evidence for elevated [Ca++]i in cerebrocortical terminals of adult rats following chronic consumption of ethanol-containing liquid diets for "neurotoxic" durations. Compared to isocaloric carbohydrate-fed controls, ethanol-fed rats had significantly higher [Ca++]i in P2 synaptosomal fractions after 4 months of diet intake, and in purified cerebrocortical synaptosomes after diet ingestion for 10 months. In addition, [Ca++]i in the synaptosomal fractions of ethanol-fed rats from either exposure time were markedly resistant to K(+)-dependent potentiation. Persistently increased synaptic [Ca++]i and a blunted response to K+ depolarization following chronic ethanol ingestion lead us to associate impaired Ca++ homeostasis in the neurodegenerative processes of alcoholism.
Collins
M A
MA
Department of Biochemistry, Loyola University of Chicago, Stritch School of Medicine, Maywood, IL 60153.
Raikoff
K
K
D000437:Alcoholism / Q000378:metabolism*; D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005456:Fluorescent Dyes; D016257:Fura-2; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D000634:Aminoquinolines; D005456:Fluorescent Dyes; C035739:Quin2; D002118:Calcium; D016257:Fura-2