TY - JOUR
T1 - The possible role of voltage-operated calcium channels in the enhancement of excitatory amino acid toxicity following chronic ethanol exposure in vitro.
AU - Ruhe, C. A.
AU - Littleton, J. M.
PY - 1994
Y1 - 1994
N2 - 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(DHP) calcium channel blocker, nicardipine, was found to significantly attenuate EAA-induced cytotoxicity in ethanol withdrawn cell cultures with all indices measured.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.
AB - 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(DHP) calcium channel blocker, nicardipine, was found to significantly attenuate EAA-induced cytotoxicity in ethanol withdrawn cell cultures with all indices measured.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.
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M3 - Article
C2 - 8974339
AN - SCOPUS:0028677865
SN - 1358-6173
VL - 2
SP - 217
EP - 221
JO - Alcohol and alcoholism (Oxford, Oxfordshire). Supplement.
JF - Alcohol and alcoholism (Oxford, Oxfordshire). Supplement.
ER -