Single-cell measurements of quantal secretion induced by alpha-latrotoxin from rat adrenal chromaffin cells: Dependence on extracellular Ca2+

alpha-Latrotoxin (alpha-LT), from black widow spider venom, is a potent enhancer of the spontaneous quantal release of neurotransmitter from a variety of nerve terminals and clonal neurosecretory cells. Using electrochemical amperometry and estimation of membrane impedance by phase detection, we present evidence that alpha-LT induces exocytosis of catecholamines from rat adrenal chromaffin cells beginning as rapidly as 30 s after close application of the toxin. This release is largely dependent on adequate levels of extracellular Ca2+ ([Ca2+](o)). Lowering [Ca2+](o) from 2 mM to less than or equal to 10-20 mu M reduces the alpha-LT-induced rise in membrane capacitance by at least sixfold, on average, and nearly abolishes alpha-LT-induced quantal amperometric events, while still permitting insertion of non-selective cation channels. Based on these experiments, we argue that the rapid onset of alpha-LT action in promoting massive quantal release from chromaffin cells is primarily due to an increase in the Ca2+ permeability of the plasma membrane through non-selective cation channels.