{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:32:46Z","timestamp":1770910366375,"version":"3.50.1"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2000,4,14]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014Pathological changes of the vasculature are characterized by changes in Ca\n            <jats:sup>2+<\/jats:sup>\n            handling and alterations in gene expression. In neurons and other cell types, [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>i<\/jats:sub>\n            often drives changes in gene expression. However, the relationship between Ca\n            <jats:sup>2+<\/jats:sup>\n            signaling and gene expression in vascular smooth muscle is not well understood. This study examines the ability of Ca\n            <jats:sup>2+<\/jats:sup>\n            influx through voltage-dependent, L-type Ca\n            <jats:sup>2+<\/jats:sup>\n            channels (VDCCs) and Ca\n            <jats:sup>2+<\/jats:sup>\n            release through ryanodine receptors (RyRs) to activate the transcription factor, cAMP-responsive element binding protein (CREB), and increase c-\n            <jats:italic>fos<\/jats:italic>\n            levels in intact cerebral arteries. Membrane depolarization increased the fraction of nuclei staining for phosphorylated CREB (P-CREB) and levels of c-\n            <jats:italic>fos<\/jats:italic>\n            mRNA in intact mouse cerebral arteries. Ryanodine, which inhibits RyRs, increased P-CREB staining and c-\n            <jats:italic>fos<\/jats:italic>\n            levels. Forskolin, an activator of adenylyl cyclase, and sodium nitroprusside, an NO donor, increased P-CREB and c-\n            <jats:italic>fos<\/jats:italic>\n            levels. Nisoldipine, an inhibitor of VDCCs, reversed the effects of depolarization and ryanodine on P-CREB and c-\n            <jats:italic>fos<\/jats:italic>\n            levels, but not the effects of forskolin or sodium nitroprusside. Inhibition of Ca\n            <jats:sup>2+<\/jats:sup>\n            \/calmodulin-dependent protein kinase (CaM kinase) blocked increases in P-CREB and c-\n            <jats:italic>fos<\/jats:italic>\n            levels seen with membrane depolarization, suggesting that CaM kinase has an important role in the pathway leading from Ca\n            <jats:sup>2+<\/jats:sup>\n            influx to CREB-mediated changes in c-\n            <jats:italic>fos<\/jats:italic>\n            levels. Our data suggest that membrane depolarization increases [Ca\n            <jats:sup>2+<\/jats:sup>\n            ]\n            <jats:sub>i<\/jats:sub>\n            through activation of VDCCs, leading to increased P-CREB and c-\n            <jats:italic>fos<\/jats:italic>\n            , and that RyRs have a profound effect on this pathway by indirectly regulating Ca\n            <jats:sup>2+<\/jats:sup>\n            entry through VDCCs. These results provide the first evidence of Ca\n            <jats:sup>2+<\/jats:sup>\n            regulation of CREB and c-\n            <jats:italic>fos<\/jats:italic>\n            in arterial smooth muscle.\n          <\/jats:p>","DOI":"10.1161\/01.res.86.7.760","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:52:16Z","timestamp":1339462336000},"page":"760-767","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":84,"title":["Coupling of Ca\n            <sup>2+<\/sup>\n            to CREB Activation and Gene Expression in Intact Cerebral Arteries From Mouse"],"prefix":"10.1161","volume":"86","author":[{"given":"L.","family":"Cartin","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, University of Vermont, Burlington, Vt."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. M.","family":"Lounsbury","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of Vermont, Burlington, Vt."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. T.","family":"Nelson","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, University of Vermont, Burlington, Vt."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","unstructured":"Berridge MJ. Elementary and global aspects of calcium signalling. J Physiol (Lond). 1997;499(pt 2):291\u2013306.","DOI":"10.1113\/jphysiol.1997.sp021927"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)31290-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(90)90115-V"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90013-5"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.4.1717"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90055-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.21.12202"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.11.5061"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/32448"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81816-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.259.1.C3"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8235594"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5236.633"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.6.C1755"},{"key":"e_1_3_2_15_2","doi-asserted-by":"crossref","unstructured":"Knot HJ Nelson MT. Regulation of arterial diameter and wall [Ca2+] in cerebral arteries of rat by membrane potential and intravascular pressure. J Physiol (Lond). 1998;508(pt 1):199\u2013209.","DOI":"10.1111\/j.1469-7793.1998.199br.x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","unstructured":"Jaggar JH Porter VA Lederer WJ Nelson MT. Calcium sparks in smooth muscle. Am J Physiol. 2000:278:C235\u2013C256.","DOI":"10.1152\/ajpcell.2000.278.2.C235"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","unstructured":"Knot HJ Standen NB Nelson MT. Ryanodine receptors regulate arterial diameter and wall [Ca2+] in cerebral arteries of rat via Ca2+-dependent K+ channels. J Physiol (Lond). 1998;508(pt 1):211\u2013221.","DOI":"10.1111\/j.1469-7793.1998.211br.x"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.14.9489"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)61094-7"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.1998.tb10706.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/44586"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.5.C1346"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.4.459"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.21.2527"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3066"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(05)80274-6"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/386855a0"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.RES.86.7.760","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T20:40:51Z","timestamp":1715546451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.RES.86.7.760"}},"subtitle":["Roles of Ryanodine Receptors and Voltage-Dependent Ca\n            <sup>2+<\/sup>\n            Channels"],"short-title":[],"issued":{"date-parts":[[2000,4,14]]},"references-count":27,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2000,4,14]]}},"alternative-id":["10.1161\/01.RES.86.7.760"],"URL":"https:\/\/doi.org\/10.1161\/01.res.86.7.760","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,4,14]]},"assertion":[{"value":"1999-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-02-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}