{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:11:05Z","timestamp":1789978265736,"version":"4.0.1"},"reference-count":47,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,6,1]]},"abstract":"<jats:p>Highly localized Ca2+ release events have been characterized in several neuronal preparations. In mouse neurohypophysial terminals (NHTs), such events, called Ca2+ syntillas, appear to emanate from a ryanodine-sensitive intracellular Ca2+ pool. Traditional sources of intracellular Ca2+ appear to be lacking in NHTs. Thus, we have tested the hypothesis that large dense core vesicles (LDCVs), which contain a substantial amount of calcium, represent the source of these syntillas. Here, using fluorescence immunolabeling and immunogold-labeled electron micrographs of NHTs, we show that type 2 ryanodine receptors (RyRs) are localized specifically to LDCVs. Furthermore, a large conductance nonspecific cation channel, which was identified previously in the vesicle membrane and has biophysical properties similar to that of an RyR, is pharmacologically affected in a manner characteristic of an RyR: it is activated in the presence of the RyR agonist ryanodine (at low concentrations) and blocked by the RyR antagonist ruthenium red. Additionally, neuropeptide release experiments show that these same RyR agonists and antagonists modulate Ca2+-elicited neuropeptide release from permeabilized NHTs. Furthermore, amperometric recording of spontaneous release events from artificial transmitter-loaded terminals corroborated these ryanodine effects. Collectively, our findings suggest that RyR-dependent syntillas could represent mobilization of Ca2+ from vesicular stores. Such localized vesicular Ca2+ release events at the precise location of exocytosis could provide a Ca2+ amplification mechanism capable of modulating neuropeptide release physiologically.<\/jats:p>","DOI":"10.1085\/jgp.201311110","type":"journal-article","created":{"date-parts":[[2014,5,26]],"date-time":"2014-05-26T14:58:16Z","timestamp":1401116296000},"page":"693-702","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Functional ryanodine receptors in the membranes of neurohypophysial secretory granules"],"prefix":"10.1085","volume":"143","author":[{"given":"James M.","family":"McNally","sequence":"first","affiliation":[{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"},{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Custer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"},{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Ortiz-Miranda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"},{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dixon J.","family":"Woodbury","sequence":"additional","affiliation":[{"name":"Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D.","family":"Kraner","sequence":"additional","affiliation":[{"name":"Department of Neuroscience 4 and 5"},{"name":"Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 4 and 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Salzberg","sequence":"additional","affiliation":[{"name":"Department of Neuroscience 4 and 5"},{"name":"Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 4 and 5"},{"name":"Department of Neuroscience 4 and 5"},{"name":"Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 4 and 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"Lemos","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"},{"name":"Department of Microbiology and Physiological Systems 1 and 2"},{"name":"Program in Neuroscience, University of Massachusetts Medical School, Worcester, MA 01655 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,5,26]]},"reference":[{"key":"2023072623143071100_bib1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/sj.bjp.0704901","article-title":"Presynaptic internal Ca2+ stores contribute to inhibitory neurotransmitter release onto mouse cerebellar Purkinje cells","volume":"137","author":"Bardo","year":"2002","journal-title":"Br. 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