BOTULINUM NEUROTOXIN LIGHT-CHAINS INHIBIT BOTH CA2-INDUCED AND CTP ANALOG-INDUCED CATECHOLAMINE RELEASE FROM PERMEABILIZED ADRENAL CHROMAFFIN CELLS()

Using digitonin-permeabilised bovine adrenal chromaffin cells, the eff ects of botulinum neurotoxin light chains on exocytosis triggered by C a2+ or by GppNHp were examined, Botulinum neurotoxin D light chain, pr epared as a His(6)-tagged recombinant protein, cleaved VAMP and substa ntially inhibited catecholamine release due to Ca2+ and GppNHp. Botuli num neurotoxin C1 and E light chains produced partial inhibition of bo th Ca2+- and GppNHp-induced catecholamine release. These results sugge st that Ca2+-dependent exocytosis and Ca2+-independent exocytosis trig gered by a non-hydrolysable GTP analogue occurs via a SNARE-dependent mechanism in chromaffin cells.