BA2-TERMINALS( IONS EVOKE 2 KINETICALLY DISTINCT PATTERNS OF EXOCYTOSIS IN CHROMAFFIN CELLS, BUT NOT IN NEUROHYPOPHYSEAL NERVE)

The coupling between divalent cations and exocytosis of large dense-co red vesicles (LDCV) was studied with capacitance-detection techniques in nerve terminals of the rat neurohypophysis (NHP) and bovine chromaf fin cells, Ba2+ substitution for Ca2+ produced kinetically distinct re sponses in the two preparations.In NHP terminals, Ba2+ ions behave as weak substitutes for Ca2+, Exocytotic events occur principally during depolarizing pulses, i.e., events are ''stimulus-coupled'' to Ba2+ ent ry through voltage-gated Ca2+ channels, Stimulus-coupled exocytosis ap parently requires elevated submembrane cation concentrations that diss ipate rapidly on hyperpolarization-induced Ca2+-channel closure. Intra cellular dialysis of NHP terminals with Ba2+ does not evoke exocytosis , nor does it interfere with depolarization-evoked Ca2+ influx and exo cytosis. In chromaffin cells, Ba2+ ions evoke a small quantity of stim ulus-coupled secretion, but the dominant response is an additional pro nounced poststimulus capacitance increase that outlasts channel closur es by 20-50 sec, ''Stimulus-decoupled'' exocytosis is slow (similar to 25-40 fF/sec) compared with Ca2+-evoked stimulus-coupled exocytosis ( similar to 1000 fF/sec), Decoupled secretion is not attributable to Ba 2+ displacement of intracellular Ca2+ ions, because it is insensitive to 10 mM EGTA or thapsigargin, Slow exocytosis is initiated by inclusi on of Ba2+ ions in the recording pipette and continues steadily for 5- 12 min, producing a total increase of several thousand fF, which ultim ately doubles or triples the original cell-surface area, We propose th at two pathways of regulated exocytosis with distinct kinetics and div alent cation sensitivity exist in chromaffin cells, Only a single kine tic pattern is detected in NHP terminals, suggesting that mechanisms f or secretion are not universally distributed in excitable cells.