Calcium loading of secretory granules in stimulated neurohypophysical nerve endings

Ca2+Syntillas, Miniature Ca2+Release Events in Terminals of Hypothalamic Neurons, Are Increased in Frequency by Depolarization in the Absence of Ca2+Influx

“…One intriguing candidate for the source of syntilla Ca 2ϩ is the neurosecretory granules in which preliminary studies using immunogold labeling have disclosed both RyRs and IP 3 Rs (Salzberg et al, 2000). Moreover, in these neurosecretory granules, Ca 2ϩ is stored at high levels that may be altered in the process of depolarizationinduced secretion (Thirion et al, 1995). However, it is not clear how these results relate to our finding that TG, which is specific for SERCA pumps, drastically reduced the frequency of syntilla because SERCA pumps are generally considered to reside only on ER membrane.…”

NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area

“…However, in the secretory granule area, the acidic Ca 2+ store is 30% larger than the ER. Whereas lysosomes have not generally been considered as organelles with a high Ca 2+ content, the secretory granules are known for their high Ca 2+ concentration (Clemente and Meldolesi, 1975;Nakagaki et al, 1984;Nicaise et al, 1992;Thirion et al, 1995;Gerasimenko et al, 1996c). Our experiments with brefeldin A would appear to exclude the Golgi, and the results with GPN to exclude the lysosomes as possible candidate organelles for the thapsigargin-insensitive Ca 2+ store.…”

Stimulus–secretion coupling in neurohypophysial nerve endings: A role for intravesicular sodium?

“…We have shown previously that if the potassium challenge was discontinued after 6 min, Ca v returned to control levels (9). If secretion was blocked (by hyperosmotic saline), Ca v decrease after the end of depolarization was not observed, suggesting that in isosmotic conditions the Ca-rich vesicles had been preferentially secreted (9). In the present work, we add the observation that after 20 min of continuous potassium challenge, the increase in Ca v is even larger than at 6 min.…”

“…This behavior contrasts with the known but mechanistically obscure secretagogue effect of Na ϩ (6)(7)(8), wherein an artificially induced increase in cytosolic Na ϩ concentration can induce a sustained and continuous secretion (8). In previous work on neurohypophysial nerve endings, one of our laboratories reported that the Ca content of the secretory vesicles increased upon secretory stimulation, and that Ca-rich vesicles accumulated when secretion was blocked (9), suggesting a role of intravesicular ion concentration in the secretory mechanism. This hypothesis is further supported by observation that in insulin-secreting cells, Ca 2ϩ depletion from secretory granules inhibits exocytosis (10).…”

“…Sci. USA 96 (1999)terminals, high cytosolic Ca, which is a known consequence of potassium depolarization, is probably at the origin of high Ca v (9,13,23). We have shown previously that if the potassium challenge was discontinued after 6 min, Ca v returned to control levels (9).…”