Synaptotagmin I is essential for Ca(2+)-independent release of neurotransmitter induced by alpha-latrotoxin.

alpha-Latrotoxin causes massive release of norepinephrine from clonal rat pheochromocytoma PC12 cells, in the absence of external Ca2+, by an unknown mechanism. The effect almost disappeared in PC12 variant cells deficient in synaptotagmin I, a synaptic vesicle protein, and was rescued by transfecting the synaptotagmin I gene. These results indicate that synaptotagmin I is essential for the Ca(2+)-independent action of alpha-latrotoxin in PC12 cells.