Ca2+ sparks and secretion in dorsal root ganglion neurons

Ca2+ sparks as the elementary intracellular Ca2+ release events are instrumental to local control of Ca2+ signaling in many types of cells. Here, we visualized neural Ca2+ sparks in dorsal root ganglion (DRG) sensory neurons and investigated possible role of DRG sparks in the regulation of secretion from the somata of the cell. DRG sparks arose mainly from type 3 ryanodine receptor Ca2+ release channels on subsurface cisternae of the endoplasmic reticulum, rendering a striking subsurface localization. Caffeine- or 3,7-dimethyl-1-(2-propynyl)xanthine-induced store Ca2+ release, in the form of Ca2+ sparks, triggered exocytosis, independently of membrane depolarization and external Ca2+. The spark-secretion coupling probability was estimated to be between 1 vesicle per 6.6 sparks and 1 vesicle per 11.4 sparks. During excitation, subsurface sparks were evoked by physiological Ca2+ entry via the Ca2+- induced Ca2+ release mechanism, and their synergistic interaction with Ca2+ influx accounted for approximate to 60% of the Ca2+-dependent exocytosis. Furthermore, inhibition of Ca2+-induced Ca2+ release abolished endotoxin-induced secretion of pain-related neuropeptides. These findings underscore an important role for Ca2+ sparks in the amplification of surface Ca2+ influx and regulation of neural secretion.