Mc. Nowycky et al., EXCITATION-SECRETION COUPLING IN MAMMALIAN NEUROHYPOPHYSEAL NERVE-TERMINALS, Cellular and molecular neurobiology, 18(1), 1998, pp. 65-80
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.