In chromaffin cells the number of large dense-core vesicles (LDCVs) which c
an be released by brief, intense stimuli represents only a small fraction o
f the 'morphologically docked' vesicles at the plasma membrane. Recently, i
t was shown that Munc13-1 is essential for a post-docking step of synaptic
vesicle fusion, To investigate the role of Munc13-1 in LDCV exocytosis, we
overexpressed Munc13-1 in chromaffin cells and stimulated secretion by flas
h photolysis of caged calcium. Both components of the exocytotic burst, whi
ch represent the fusion of release-competent vesicles, were increased by a
factor of three. The sustained component, which represents vesicle maturati
on and subsequent fusion, was increased by the same factor. The response to
a second flash, however, was greatly reduced, indicating a depletion of re
lease-competent vesicles. Since there was no apparent change in the number
of docked vesicles, we conclude that Munc13-1 acts as a priming factor by a
ccelerating the rate constant of vesicle transfer from a pool of docked, bu
t unprimed vesicles to a pool of release-competent, primed vesicles.