Ca2+ sparks and secretion in dorsal root ganglion neurons.
Ca(2+) sparks as the elementary intracellular Ca(2+) release events are instrumental to local control of Ca(2+) signaling in many types of cells. Here, we visualized neural Ca(2+) 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 Ca(2+) 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 Ca(2+) release, in the form of Ca(2+) sparks, triggered exocytosis, independently of membrane depolarization and external Ca(2+). 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 Ca(2+) entry via the Ca(2+)-induced Ca(2+) release mechanism, and their synergistic interaction with Ca(2+) influx accounted for approximately 60% of the Ca(2+)-dependent exocytosis. Furthermore, inhibition of Ca(2+)-induced Ca(2+) release abolished endotoxin-induced secretion of pain-related neuropeptides. These findings underscore an important role for Ca(2+) sparks in the amplification of surface Ca(2+) influx and regulation of neural secretion.
Ouyang
Kunfu
K
Institute of Molecular Medicine and National Laboratory of Biomembrane and Membrane Biotechnology, Peking University, Beijing, China.
Zheng
Hui
H
Qin
Xiaomei
X
Zhang
Chen
C
Yang
Dongmei
D
Wang
Xian
X
Wu
Caihong
C
Zhou
Zhuan
Z
Cheng
Heping
H
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology
D019837:Ryanodine Receptor Calcium Release Channel; D002110:Caffeine; C057837:3,7-dimethyl-1-propargylxanthine; D015740:Calcitonin Gene-Related Peptide; D013805:Theobromine; D002118:Calcium