{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:46:04Z","timestamp":1791326764697,"version":"4.3.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"46","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,11,18]]},"abstract":"Significance<\/jats:title>\n \n The heart contracts more forcefully in response to fear, stress, or exercise through the fight-or-flight response. This physiological process is mediated by \u03b2-adrenergic receptors acting through adenylyl cyclase, cAMP, and cAMP-dependent protein kinase (PKA), which phosphorylates the cardiac calcium channel Ca\n V<\/jats:sub>\n 1.2 and increases its activity. We show that mutation of a single amino acid residue, Ser-1700, in a PKA phosphorylation site at the interface between the distal and proximal C-terminal domains substantially disrupts this regulatory mechanism in mice. Basal and \u03b2-adrenergic\u2013stimulated calcium currents, myocyte contractility, and stress-induced exercise capacity are all reduced. Moreover, these mice develop cardiac hypertrophy, an indication of failure of cardiac homeostasis in vivo. Evidently, phosphorylation of Ser-1700 is a primary event in cardiovascular regulation.\n <\/jats:p>","DOI":"10.1073\/pnas.1419129111","type":"journal-article","created":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T03:14:46Z","timestamp":1415070886000},"page":"16598-16603","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Basal and \u03b2-adrenergic regulation of the cardiac calcium channel Ca\n V<\/sub>\n 1.2 requires phosphorylation of serine 1700"],"prefix":"10.1073","volume":"111","author":[{"given":"Ying","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Washington, Seattle, WA 98195-7280"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Westenbroek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Washington, Seattle, WA 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