Editors' ChoiceSECRETION

Moving Closer to the Trigger Zone

Science's STKE  05 Aug 2003:
Vol. 2003, Issue 194, pp. tw302-TW302
DOI: 10.1126/stke.2003.194.tw302

Evoked release of hormones and neurotransmitter depends on influx of calcium (Ca2+) through voltage-gated Ca2+ channels, as do various forms of use-dependent changes in the efficacy of transmitter release. Ca2+ influx leads to transient submembrane microdomains of high Ca2+ concentration [Ca2+]; the spatial relation between these microdomains and vesicles containing hormones or neurotransmitter influences the dynamics of secretion. The precise details of Ca2+-triggered exocytosis, however, have remained unclear. Becherer et al. used dual-wavelength evanescent field microscopy to monitor the spatiotemporal relation between submembrane Ca2+ microdomains and exocytosis from single chromaffin granules in bovine chromaffin cells. [Ca2+] was monitored with a low-affinity indicator (fluo-5), and chromaffin cells were labeled with an acidophilic dye. The authors visualized brief, spatially confined [Ca2+] spikes whose frequency was increased by depolarization with high potassium (which also increased amperometrically measured catecholamine release). These Ca2+ microdomains selectively triggered the release of vesicles that were docked nearby (within 300 nm). Only a fraction of such vesicles, however, were released by a nearby Ca2+ spike. There was no correlation between Ca2+ spike amplitude and vesicle release for vesicles within the release zone. After stimulation, more vesicles were located within the range of the Ca2+ "release trigger." These data suggest the existence of a pool of docked vesicles that are not yet ready to be released; the stimulation-dependent increase in the number of vesicles in the trigger zone presents a potential mechanism for use-dependent facilitation of release.

U. Becherer, T. Moser, W. Stühmer, M. Oheim, Calcium regulates exocytosis at the level of single vesicles. Nat. Neurosci. 6, 846-853 (2003). [Online Journal]