PT - JOURNAL ARTICLE AU - EP Seward AU - NI Chernevskaya AU - MC Nowycky TI - Ba2+ ions evoke two kinetically distinct patterns of exocytosis in chromaffin cells, but not in neurohypophysial nerve terminals AID - 10.1523/JNEUROSCI.16-04-01370.1996 DP - 1996 Feb 15 TA - The Journal of Neuroscience PG - 1370--1379 VI - 16 IP - 4 4099 - http://www.jneurosci.org/content/16/4/1370.short 4100 - http://www.jneurosci.org/content/16/4/1370.full SO - J. Neurosci.1996 Feb 15; 16 AB - The coupling between divalent cations and exocytosis of large dense- cored vesicles (LDCV) was studied with capacitance-detection techniques in nerve terminals of the rat neurohypophysis (NHP) and bovine chromaffin cells. Ba2+ substitution for Ca2+ produced kinetically distinct responses 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+ entry through voltage-gated Ca2+ channels. Stimulus- coupled exocytosis apparently requires elevated submembrane cation concentrations that dissipate rapidly on hyperpolarization-induced Ca(2+)-channel closure. Intracellular dialysis of NHP terminals with Ba2+ does not evoke exocytosis, nor does it interfere with depolarization-evoked Ca2+ influx and exocytosis. In chromaffin cells, Ba2+ ions evoke a small quantity of stimulus-coupled secretion, but the dominant response is an additional pronounced poststimulus capacitance increase that outlasts channel closures by 20–50 sec. “Stimulus- decoupled” exocytosis is slow (approximately 25–40 fF/sec) compared with Ca(2+)-evoked stimulus-coupled exocytosis (approximately 1000 fF/sec). Decoupled secretion is not attributable to Ba2+ displacement of intracellular Ca2+ ions, because it is insensitive to 10 mM EGTA or thapsigargin. Slow exocytosis is initiated by inclusion of Ba2+ ions in the recording pipette and continues steadily for 5–12 min, producing a total increase of several thousand fF, which ultimately doubles or triples the original cell-surface area. We propose that two pathways of regulated exocytosis with distinct kinetics and divalent cation sensitivity exist in chromaffin cells. Only a single kinetic pattern is detected in NHP terminals, suggesting that mechanisms for secretion are not universally distributed in excitable cells.