The possible role of voltage-operated calcium channels in the enhancement of excitatory amino acid toxicity following chronic ethanol exposure in vitro.
It is well established that ethanol withdrawal is associated with hyperexcitability of central neurons, and that the increased responsiveness demonstrated to excitatory amino acids (EAAs) may contribute to the physical signs of ethanol withdrawal and to neurodegeneration. Although the mechanisms of neuronal hyperexcitation are not fully understood, there is considerable evidence to suggest an increase in both NMDA receptors and voltage operated calcium channels (VOCCs) may play an important role. Cultures of bovine adrenal chromaffin cells (BACCs) and fetal rat neocortical neurons chronically treated with ethanol showed enhanced toxicity when challenged with various EAAs. Quantitative assessment of cell survival was determined by catecholamine release (CA), and fluorescein diacetate (FDA) staining in BACCs, and lactate dehydrogenase (LDH) release in cortical neurons. The dihydropyridine (DHP) calcium channel blocker, nicardipine, was found to significantly attenuate EAA-induced cytotoxicity in ethanol withdrawn cell cultures with all indices measured. These results suggest that increased Ca2+ influx through VOCCs and NMDA receptors may each contribute to ethanol-mediated neurodegeneration.
Ruhe
C A
CA
Division of Biomedical Science, King's College, London, U.K.
Littleton
J M
JM
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D018846:Excitatory Amino Acids / Q000633:toxicity*; D005973:Glutamine / Q000633:toxicity; D009410:Nerve Degeneration / Q000187:drug effects; D009529:Nicardipine / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018846:Excitatory Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D000431:Ethanol; D009529:Nicardipine