Reduced Ca2+ flux in synaptosomes from cats with GM1 gangliosidosis

Ca2+ transport was studied in synaptosomes prepared from normal cats and cats with GM1 gangliosidosis. The influx of Ca2+ was found to be a biphasic process in synaptosomes from both GM1 mutant and normal cats. Both the fast and slow phases of voltage-dependent Ca2+ uptake were significantly reduced in cats with the lysosomal storage disease, however the inhibitory mechanisms differed. The fast phase of Ca2+ uptake was inhibited uncompetitively, whereas the slow phase was inhibited competitively. In addition, Na+-dependent Ca2+ efflux was reduced significantly in cats with GM1 gangliosidosis. Since it is well established that maintenance of Ca2+ homeostasis is essential for normal neuronal function, a ganglioside-induced disruption of Ca2+ transport across synaptic membranes may be responsible, in part, for the neuronal dysfunction characteristic of GM1 gangliosidosis.