Brain damage occurs in over 60% of chronic alcoholics. The causes an pathophysiology of this damage, however, are poorly understood. The general goal of our research has been to evaluate the factors that lead to alcohol-induced degeneration of the nervous system in experimental animals. Ethanol has been shown to release calcium from intracellular storage sites (U. Pande and H.C. Pant, Neuroscience 9: 1235, 1983; J.B. Hoek and E. Rubin 13th International Congress of Biochem. 28, 1985). The increase in cytosolic calcium activates proteases cause proteolysis of cytoskeletal proteins. The possibility exist that some of the effects of alcohol-induced degeneration may be to the activation of these proteases. In order to investigate the role of intracellular calcium during neuronal degeneration we have used the squid giant axon as a model system. The advantages of using this preparation are that the enzyme and substrates can be extruded in high yield from the giant axon, thus avoiding contamination of the preparation with nonaxonal enzymes, which may become nonspecifically attached during the homogenization of whole tissue. Second, enzyme activities and substrates present in axoplasm and axoplasmic preparations can e compared with the activities and substrates present in the region of the stellite ganglion, which contains the cell bodies of the giant axon. In the squid axon and cell body we have identified a number of immunoreactive degradation products after calcium-activated proteolysis. The results suggest that an elevation of cytosolic ionized calcium may result in a breakdown of proteins.
