{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:03:37Z","timestamp":1791270217508,"version":"4.1.0"},"reference-count":37,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[1998,2,1]]},"abstract":"<jats:p>Potentiation of insulin secretion from pancreatic \u03b2-cells by acetylcholine requires ongoing cyclic electrical activity initiated by other depolarizing secretagogues. Patch-clamp recordings in glucose-free solutions were made from the clonal \u03b2-cell line HIT-T15 to determine whether the muscarinic agonist bethanechol (BCh) modulated voltage-dependent Ca<jats:sup>2+<\/jats:sup>channels independent of effects on membrane potential. Only high-threshold, dihydropyridine-sensitive (L-type) Ca<jats:sup>2+<\/jats:sup>channels with a mean conductance of 26 pS were observed in cell-attached patches. BCh (100 \u03bcM) caused a two- to threefold increase in both fractional open time and mean current of single Ca<jats:sup>2+<\/jats:sup>channels. These changes resulted from a 44% decrease in the longer of two apparent mean closed times and a 25% increase in the mean open time. Similar BCh-stimulated increases in macroscopic Ca<jats:sup>2+<\/jats:sup>currents were recorded in whole cell, perforated-patch recordings. The role of protein kinase C (PKC) in the muscarinic activation of Ca<jats:sup>2+<\/jats:sup>channels was tested using a variety of PKC activators and inhibitors. Acute application of either the active phorbol ester phorbol 12-myristate 13-acetate (PMA) or the membrane-permeable diacylglycerol analog 1,2-didecanoyl- rac-glycerol mimicked the effects of BCh, whereas an inactive phorbol (4\u03b1) had no effect. Depletion of PKC activity by chronic exposure to PMA or acute application of the PKC inhibitor staurosporine greatly reduced or abolished muscarinic activation of Ca<jats:sup>2+<\/jats:sup>channels. These results are consistent with muscarinic activation of L-type, voltage-dependent Ca<jats:sup>2+<\/jats:sup>channels mediated in large part by PKC.<\/jats:p>","DOI":"10.1152\/ajpgi.1998.274.2.g397","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T09:17:56Z","timestamp":1514107076000},"page":"G397-G405","source":"Crossref","is-referenced-by-count":6,"title":["Muscarinic modulation of voltage-dependent Ca<sup>2+<\/sup>channels in insulin-secreting HIT-T15 cells"],"prefix":"10.1152","volume":"274","author":[{"given":"Jeffrey A.","family":"Love","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216; and Departments of Internal Medicine and Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil W.","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216; and Departments of Internal Medicine and Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung","family":"Owyang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216; and Departments of Internal Medicine and Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Dawson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216; and Departments of Internal Medicine and Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/363356a0"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.11.030188.000525"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/BF00373633"},{"issue":"31","key":"B4","first-page":"E336","volume":"268","author":"Boschero A. C.","year":"1995","journal-title":"Am. J. Physiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/endo-121-3-1025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/diab.30.7.558"},{"issue":"27","key":"B7","first-page":"E348","volume":"264","author":"Dukes I. D.","year":"1993","journal-title":"Am. J. Physiol."},{"key":"B8","doi-asserted-by":"crossref","first-page":"14938","DOI":"10.1016\/S0021-9258(18)77207-4","volume":"265","author":"Easom R. A.","year":"1990","journal-title":"J. Biol. Chem."},{"issue":"4","key":"B9","first-page":"E493","volume":"235","author":"Gagerman E.","year":"1978","journal-title":"Am. J. Physiol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.9893"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1042\/bj2540211"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/endo-122-5-2134"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.2.198"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/endo-120-5-1765"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0010013"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1042\/bj2670227"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.2.188"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)62101-9"},{"key":"B19","first-page":"91","volume":"10","author":"Meissner H. P.","year":"1980","journal-title":"Horm. Metab. Res. Suppl."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1986.66.4.887"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1985.248.5.C527"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(91)90231-L"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1042\/bj2640753"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.7.874"},{"key":"B25","doi-asserted-by":"crossref","first-page":"15003","DOI":"10.1016\/S0021-9258(18)77215-3","volume":"265","author":"Regazzi R.","year":"1990","journal-title":"J. Biol. Chem."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(88)80719-1"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)80669-6"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585619"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.6.C1781"},{"key":"B30","first-page":"407","volume":"216","author":"Sher E.","year":"1992","journal-title":"Eur. J. Physiol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/342550a0"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1042\/bj2650777"},{"issue":"34","key":"B33","first-page":"E65","volume":"271","author":"Verspohl E. J.","year":"1996","journal-title":"Am. J. Physiol."},{"key":"B34","doi-asserted-by":"crossref","first-page":"8314","DOI":"10.1016\/S0021-9258(19)83914-5","volume":"261","author":"Wollheim C. B.","year":"1986","journal-title":"J. Biol. Chem."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1988.tb03090.x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1981.61.4.914"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1042\/bj2790807"}],"container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpgi.1998.274.2.G397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T04:36:55Z","timestamp":1660192615000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpgi.1998.274.2.G397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,2,1]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1998,2,1]]}},"alternative-id":["10.1152\/ajpgi.1998.274.2.G397"],"URL":"https:\/\/doi.org\/10.1152\/ajpgi.1998.274.2.g397","relation":{},"ISSN":["0193-1857","1522-1547"],"issn-type":[{"value":"0193-1857","type":"print"},{"value":"1522-1547","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,2,1]]}}}