Beta-bungarotoxin-induced cell-death of neurons in chick retina.
The cytotoxicity of beta-bungarotoxin (beta-BTX), a snake venom neurotoxin with phospholipase A2 activity, for chick neurons was investigated using organ and monolayer cultures of retina. Beta-BTX led to a marked reduction in the total activities of choline acetyltransferase and glutamate decarboxylase of retina cultures at concentrations as low as 100 pM. The total activity of lactate dehydrogenase was, however, much less affected by beta-BTX. Also, the total activity of tyrosine hydroxylase of organ-cultured retina decreased only at 30-50 fold higher concentrations of the toxin. The total activity of the glial marker glutamine synthetase was not changed by beta-BTX. In contrast to this selectivity for neurons displayed by beta-BTX, non-neurotoxic phospholipases A2 from bee venom and porcine pancreas led to a simultaneous loss of both neuronal and glial marker enzymes. Light and electron microscopy of organ-cultured retina showed that only cells in the ganglion cell layer and the inner third of the amacrine cell layer degenerated after incubation with beta-BTX. In the toxin-sensitive cells, the Golgi apparatus and the endoplasmatic reticulum appeared the first subcellular structures to be affected. It is concluded that beta-BTX preferentially recognizes and/or destroys cholinergic and GABAergic cells in the amacrine and ganglion cell layers of the developing chick retina. This toxin may thus be a useful probe to investigate cell surface properties of cholinergic and GABAergic neurons in the chick central nervous system.
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D002645:Chickens; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D009410:Nerve Degeneration / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D009924:Organ Culture Techniques; D010741:Phospholipases A / Q000494:pharmacology; D054467:Phospholipases A2; D012160:Retina / Q000187:drug effects* / Q000201:enzymology; D012165:Retinal Ganglion Cells / Q000187:drug effects
D002038:Bungarotoxins; D007770:L-Lactate Dehydrogenase; D002795:Choline O-Acetyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2; D005968:Glutamate Decarboxylase