Calcium influx accompanies but does not cause excitotoxin-induced neuronal necrosis in retina.
Several authors have recently proposed that excessive calcium (Ca++) influx into postsynaptic cells may be the mechanism by which excitotoxins such as glutamate (Glu), N-methylaspartate (NMA) and kainic acid (KA) cause neuronal necrosis. Here we have undertaken both in vivo and in vitro studies to explore this hypothesis. Our findings indicate that Ca++ does accumulate selectively in neural elements undergoing degeneration in the in vivo mouse hypothalamus following subcutaneous administration of NMA. However, pretreatment with the putative Ca++ channel blocker nimodipine resulted in augmentation rather than suppression of the toxic action of NMA and Glu on the mouse hypothalamus and eliminating Ca++ from the incubation medium did not interfere with the toxic action of Glu, NMA or KA on the chick embryo retina in vitro. We conclude, therefore, that Ca++ influx is an unlikely explanation for excitotoxin-induced degeneration of retinal or hypothalamic neurons.
Price
M T
MT
Olney
J W
JW
Samson
L
L
Labruyere
J
J
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D016202:N-Methylaspartate; D009336:Necrosis; D009539:Nicotinic Acids / Q000494:pharmacology; D009553:Nimodipine; D011759:Pyrrolidines / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
D005971:Glutamates; D009539:Nicotinic Acids; D011759:Pyrrolidines; D001224:Aspartic Acid; D018698:Glutamic Acid; D009553:Nimodipine; D016202:N-Methylaspartate; D007608:Kainic Acid; D002118:Calcium