EXCITATION-SECRETION COUPLING IN MAMMALIAN NEUROHYPOPHYSEAL NERVE-TERMINALS

1. Oxytocin and vasopressin secretion from the neurohypophysis (NHP) i s evoked by strongly patterned bursts of action potentials. We studied excitation-secretion coupling in single isolated terminals of rat NHP using patch clamp and capacitance detection techniques, 2. The secret ory response evoked by trains of depolarizing pulses consisted of two discrete phases, Ca2+ entry during pulses early in the train did not e licit secretion. Exocytotic responses began only after a characteristi c amount of total Ca2+ entry called ''threshold.'' 3. In the postthres hold secretory phase, exocytotic events occurred during or immediately after depolarizing pulses, indicating that the final Ca2+-dependent s tep is triggered by high Ca2+ concentrations near the plasma membrane that dissipate rapidly after channel closure, Secretion was sensitive to both the concentration and species of Ca2+ chelator. BAPTA, a Ca2chelator with rapid Ca2+ binding kinetics, was more effective than EGT A in diminishing secretion, 4. The ''threshold'' amount of Ca2+ was de termined by the concentration, but not species, of Ca2+ chelator. The threshold value was constant even when Ca2+ entry parameters were vari ed over a broad range of current amplitudes, pulse durations, and numb er of pulses, indicating that it did not require high Ca2+ concentrati ons near the plasma membrane. 5. These results suggest that the secret ory response to a train of pulses consists of a Ca2+-dependent prepara tory step that must be completed before subsequent Ca2+ entry can elic it exocytosis. 6. Exocytotic responses during single trains showed str ong depression at a step subsequent to Ca2+ entry. Recovery from depre ssion required 30-60 sec. 7. The properties of threshold secretion obs erved in NHP terminals are discussed in terms of current models of sec retion.