{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T06:16:34Z","timestamp":1779344194992,"version":"3.51.4"},"reference-count":59,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[1995,7,1]],"date-time":"1995-07-01T00:00:00Z","timestamp":804556800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>When stimulated by the cholinergic agonist carbachol, PC12 cells rapidly secrete a large fraction of the intracellular catecholamines by exocytotic release from the large dense-core secretory vesicles in a Ca2+-dependent manner. To investigate whether Ca2+\/calmodulin kinase II plays a role in the regulated secretion of catecholamines, we examined the effect of the specific Ca2+\/calmodulin kinase II inhibitor KN-62 on the carbachol-induced release of norepinephrine from PC12 cells. Approximately 50% of the regulated release of norepinephrine, stimulated either by carbachol or direct depolarization, was inhibited by pretreatment with KN-62, while the remaining 50% was resistant to KN-62 and therefore independent of Ca2+\/calmodulin kinase II. In contrast, H7, an inhibitor of protein kinase C, had no effect on any of the stimulated release. FURA 2 imaging experiments demonstrated that KN-62 does not act by blocking the stimulation-induced increase in intracellular [Ca2+]. The most likely model consistent with these data is that all the dense-core vesicles fuse with the plasma membrane in a Ca2+-dependent process, but that approximately 50% of the vesicles require an additional step that is dependent on the action of Ca2+\/calmodulin kinase II. This step occurs between the influx of Ca2+ and the fusion of vesicle membranes with the plasma membrane, and may be analogous to the Ca2+\/calmodulin kinase II phosphorylation of synapsin which mobilizes small, clear synaptic vesicles for exocytosis at the synapse.<\/jats:p>","DOI":"10.1242\/jcs.108.7.2619","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T02:41:16Z","timestamp":1619232076000},"page":"2619-2628","source":"Crossref","is-referenced-by-count":30,"title":["Inhibition of regulated catecholamine secretion from PC12 cells by the Ca2+\/Calmodulin kinase II inhibitor KN-62"],"prefix":"10.1242","volume":"108","author":[{"given":"Erik S.","family":"Schweitzer","sequence":"first","affiliation":[{"name":"1 Departments of Anatomy and Cell Biology, and UCLA School of Medicine, Los Angeles, CA 90024, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Sanderson","sequence":"additional","affiliation":[{"name":"1 Departments of Anatomy and Cell Biology, and UCLA School of Medicine, Los Angeles, CA 90024, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. G.","family":"Wasterlain","sequence":"additional","affiliation":[{"name":"1 Departments of Anatomy and Cell Biology, and UCLA School of Medicine, Los Angeles, CA 90024, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1995,7,1]]},"reference":[{"key":"2023122621535380200_JOCES_108_7_2619C1","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1111\/j.1471-4159.1984.tb12742.x","article-title":"Chromaffin granule membrane-F-actin interactions and spectrin-like protein of subcellular organelles: a possible relationship","volume":"42","author":"Aunis","year":"1984","journal-title":"J. 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