{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T17:28:12Z","timestamp":1788197292934,"version":"build-2803163510"},"reference-count":55,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:p> Neonatal rat cardiac myocytes were exposed to 10 nM thapsigargin (TG) or 20 \u03bcM phenylephrine (PE) to compare resulting alterations of Ca<jats:sup>2+<\/jats:sup> homeostasis. Either treatment results in resting cytosolic [Ca<jats:sup>2+<\/jats:sup>] rise and reduction of Ca<jats:sup>2+<\/jats:sup> signals in myocytes following electrical stimuli. In fact, ATP-dependent Ca<jats:sup>2+<\/jats:sup> transport is reduced due to catalytic inhibition of sarcoplasmic reticulum ATPase (SERCA2) by TG or reduction of SERCA2 protein expression by PE. A marked rise of nuclear factor of activated T cells (NFAT)-dependent expression of transfected luciferase cDNA is produced by TG or PE, which is dependent on increased NFAT dephosphorylation by activated calcineurin (\u2191CN) and reduced phosphorylation by inactivated glycogen synthase kinase 3\u03b2 (\u2193GSK3\u03b2). Expression of SERCA2 (inactivated) protein is increased following exposure to TG, whereas no hypertrophy is produced. On the contrary, SERCA2 expression is reduced, despite high CN activity, following protein kinase C (PKC) activation by PE (or phorbol 12-myristate 13-acetate) under conditions producing myocyte hypertrophy. Both effects of TG and PE are dependent on NFAT dephosphorylation by CN, as demonstrated by CN inhibition with cyclosporine (CsA). However, the hypertrophy program triggered by PKC activation bypasses SERCA2 transcription and expression due to competitive recruitment of NFAT and\/or other transcriptional factors. A similar dependence on CN activation, but relative reduction under conditions of PKC activation, involves transcription and expression of the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger-1. On the other hand, significant upregulation of transient receptor potential channel proteins is noted following PKC activation. The observed alterations of Ca<jats:sup>2+<\/jats:sup> homeostasis may contribute to development of contractile failure. <\/jats:p>","DOI":"10.1152\/ajpcell.00594.2008","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T02:46:42Z","timestamp":1235616402000},"page":"C992-C1002","source":"Crossref","is-referenced-by-count":24,"title":["Effects of thapsigargin and phenylephrine on calcineurin and protein kinase C signaling functions in cardiac myocytes"],"prefix":"10.1152","volume":"296","author":[{"given":"Anand Mohan","family":"Prasad","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Inesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Allo SN, McDermott PJ, Carl LL, Morgan HE. 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