Chronic alcohol reduces calcium signaling elicited by glutamate receptor stimulation in developing cerebellar neurons.
The effect of chronic alcohol (33 mM ethanol) on Ca2+ signals elicited by glutamate receptor agonists (quisqualate and NMDA) was examined in developing cerebellar Purkinje and granule neurons in culture. The neurons were exposed to alcohol during the second week in culture, the main period of morphological and physiological development. The Ca2+ signals were measured with fura-2 based microscopic video imaging. Chronic exposure to alcohol during development significantly reduced the peak amplitude of the Ca2+ signals to quisqualate (1 microM; Quis) in both the somatic and dendritic regions of the Purkinje neurons. The dendritic region was affected to a greater extent than the somatic region. Granule neurons also showed a reduced somatic Ca2+ signal to Quis (dendrites not measured) in the alcohol-treated cultures, indicating that the effect was not limited to Purkinje neurons. In addition to the effects on in the response to Quis, the peak amplitude of the Ca2+ signals to NMDA (100 microM) was reduced by chronic alcohol exposure during development in both the cultured Purkinje and granule neurons. Resting Ca2+ levels were not consistently affected by alcohol treatment in either neuronal type. These results indicate that Ca2+ signaling linked to glutamate receptor activation is an important target of alcohol in the developing nervous system and could be a contributing factor in the altered CNS function and development observed in animal models of fetal alcohol syndrome.
Gruol
D L
DL
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Parsons
K L
KL
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects*; D013997:Time Factors
D017470:Receptors, Glutamate; D000431:Ethanol; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002118:Calcium