Suppression of Ca2+ syntillas increases spontaneous exocytosis in mouse adrenal chromaffin cells
Authors
Lefkowitz, Jason J.Fogarty, Kevin E.
Lifshitz, Lawrence M.
Bellve, Karl D.
Tuft, Richard A.
ZhuGe, Ronghua
Walsh, John V. Jr.
De Crescenzo, Valerie
Document Type
Journal ArticlePublication Date
2009-10-01Keywords
Adrenal GlandsCalcium
Calcium Signaling
Chromaffin Cells
Exocytosis
Neurons
Ryanodine Receptor Calcium Release Channel
Synaptic Membranes
Neuroscience and Neurobiology
Physiology
Metadata
Show full item recordAbstract
A central concept in the physiology of neurosecretion is that a rise in cytosolic [Ca(2+)] in the vicinity of plasmalemmal Ca(2+) channels due to Ca(2+) influx elicits exocytosis. Here, we examine the effect on spontaneous exocytosis of a rise in focal cytosolic [Ca(2+)] in the vicinity of ryanodine receptors (RYRs) due to release from internal stores in the form of Ca(2+) syntillas. Ca(2+) syntillas are focal cytosolic transients mediated by RYRs, which we first found in hypothalamic magnocellular neuronal terminals. (scintilla, Latin for spark; found in nerve terminals, normally synaptic structures.) We have also observed Ca(2+) syntillas in mouse adrenal chromaffin cells. Here, we examine the effect of Ca(2+) syntillas on exocytosis in chromaffin cells. In such a study on elicited exocytosis, there are two sources of Ca(2+): one due to influx from the cell exterior through voltage-gated Ca(2+) channels, and that due to release from intracellular stores. To eliminate complications arising from Ca(2+) influx, we have examined spontaneous exocytosis where influx is not activated. We report here that decreasing syntillas leads to an increase in spontaneous exocytosis measured amperometrically. Two independent lines of experimentation each lead to this conclusion. In one case, release from stores was blocked by ryanodine; in another, stores were partially emptied using thapsigargin plus caffeine, after which syntillas were decreased. We conclude that Ca(2+) syntillas act to inhibit spontaneous exocytosis, and we propose a simple model to account quantitatively for this action of syntillas.Source
J Gen Physiol. 2009 Oct;134(4):267-80. Link to article on publisher's websiteDOI
10.1085/jgp.200910285Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44185PubMed ID
19786582Notes
Co-author Jason J. Lefkowitz is a student in the Neuroscience program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1085/jgp.200910285