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

 α-Latrotoxin (α-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 α-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 ≤ 10–20 μM reduces the α-LT-induced rise in membrane capacitance by at least sixfold, on average, and nearly abolishes α-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 α-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. Received: 22 April 1996 / Accepted: 10 June 1996