{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:38:41Z","timestamp":1791092321784,"version":"4.1.0"},"reference-count":51,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Aldosterone elevates Na+\/K+\/2Cl\u2212 cotransporter activity in rabbit cardiomyocytes within 15 min, an effect blocked by K-canrenoate and thus putatively mineralocorticoid receptor mediated. Increased cotransporter activity raises intracellular [Na+] sufficient to produce a secondary increase in Na+-K+ pump activity; when this increase in intracellular [Na+] is prevented, a rapid effect of aldosterone to lower pump activity is seen. Addition of transcription inhibitor actinomycin D did not change basal or aldosterone-induced lowered pump activity, indicating a direct, nongenomic action of aldosterone. We examined a possible role for protein kinase C (PKC) in the rapid nongenomic effects of aldosterone. Single ventricular myocytes and pipette solutions containing 10 mm intracellular [Na+] were used in patch clamp studies to measure Na+-K+ pump activity. Aldosterone lowered pump current, an effect abolished by \u03b5 PKC (\u03b5PKC) inhibition but neither \u03b1PKC nor scrambled \u03b5PKC; addition of \u03b5PKC activator peptide mimicked the rapid aldosterone effect. In rabbits chronically infused with aldosterone, the lowered pump current in cardiomyocytes was acutely (\u226415 min) restored by \u03b5PKC inhibition. These studies show that rapid effects of aldosterone on Na+-K+ pump activity are nongenomic and specifically \u03b5PKC mediated; in addition, such effects may be prolonged (7 d) and long-lived (\u223c4 h isolated cardiomyocyte preparation time). The rapid, prolonged, long-lived effects can be rapidly (\u226415 min) reversed by \u03b5PKC blockade, suggesting a hitherto unrecognized complexity of aldosterone action in the heart and perhaps by extension other tissues.<\/jats:p>","DOI":"10.1210\/en.2003-1137","type":"journal-article","created":{"date-parts":[[2003,11,11]],"date-time":"2003-11-11T01:13:38Z","timestamp":1068513218000},"page":"773-780","source":"Crossref","is-referenced-by-count":97,"title":["Rapid, Nongenomic Effects of Aldosterone in the Heart Mediated by \u03b5 Protein Kinase C"],"prefix":"10.1210","volume":"145","author":[{"given":"Anastasia S.","family":"Mihailidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahidi","family":"Mardini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Funder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613091498600_R1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1006\/bbrc.1996.0866","article-title":"Nongenomic effects of aldosterone on intracellular pH in vascular smooth muscle cells.","volume":"223","author":"Wehling","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071613091498600_R2","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1161\/01.HYP.35.5.1099","article-title":"Role of 11\u03b2-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries.","volume":"35","author":"Alzamora","year":"2000","journal-title":"Hypertension"},{"key":"2020071613091498600_R3","doi-asserted-by":"crossref","first-page":"C175","DOI":"10.1152\/ajpcell.1998.274.1.C175","article-title":"Sodium influx and Na+-K+ pump activation during short-term exposure of cardiac myocytes to aldosterone","volume":"274","author":"Mihailidou","year":"1998","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071613091498600_R3A","first-page":"263","article-title":"Rapid effects of aldosterone on cardiac Na+-K+ pump function.","volume":"82","author":"Mihailidou","year":"2002","journal-title":"Biophys J"},{"key":"2020071613091498600_R4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1161\/01.RES.86.1.37","article-title":"Hyperaldosteronemia in rabbits inhibits the cardiac sarcolemmal Na+-K+ pump.","volume":"86","author":"Mihailidou","year":"2000","journal-title":"Circ Res"},{"key":"2020071613091498600_R5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1139\/y99-041","article-title":"Na+, K+ pump and Na+ coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C.","volume":"77","author":"Gagnon","year":"1999","journal-title":"Can J Physiol Pharmacol"},{"key":"2020071613091498600_R6","doi-asserted-by":"crossref","first-page":"C541","DOI":"10.1152\/ajpcell.2000.279.3.C541","article-title":"Mechanisms of sodium pump regulation","volume":"279","author":"Therien","year":"2000","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071613091498600_R7","doi-asserted-by":"crossref","first-page":"L429","DOI":"10.1152\/ajplung.2000.279.3.L429","article-title":"Protein kinase C isozymes and the regulation of diverse cell responses","volume":"279","author":"Dempsey","year":"2000","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2020071613091498600_R8","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1161\/01.RES.86.11.1173","article-title":"Cardiotrophic effects of protein kinase C\u03b5.","volume":"86","author":"Mochly-Rosen","year":"2000","journal-title":"Circ Res"},{"key":"2020071613091498600_R9","doi-asserted-by":"crossref","first-page":"C1632","DOI":"10.1152\/ajpcell.1997.273.5.C1632","article-title":"Antisense oligodeoxynucleotide to PKC-\u03b4 blocks \u03b11-adrenergic activation of Na-K-2Cl cotransport","volume":"273","author":"Liedtke","year":"1997","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071613091498600_R10","doi-asserted-by":"crossref","first-page":"L739","DOI":"10.1152\/ajplung.2001.280.4.L739","article-title":"Differential regulation of Cl\u2212 transport proteins by PKC in Calu-3 cells","volume":"280","author":"Liedtke","year":"2001","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2020071613091498600_R11","doi-asserted-by":"crossref","first-page":"C1059","DOI":"10.1152\/ajpcell.2001.281.3.C1059","article-title":"Protein kinase C\u03b5 contributes to regulation of the sarcolemmal Na+-K+ pump","volume":"281","author":"Buhagiar","year":"2001","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071613091498600_R12","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1091\/mbc.01-07-0323","article-title":"Dopamine-induced exocytosis of Na, K-ATPase is dependent on activation of protein kinase C-\u03b5 and -\u03b4.","volume":"13","author":"Ridge","year":"2002","journal-title":"Mol Biol Cell"},{"key":"2020071613091498600_R13","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/bbrc.1995.2106","article-title":"Rapid aldosterone signaling in vascular smooth muscle cells: involvement of phospholipase C, diaglycerol and protein kinase C\u03b1.","volume":"213","author":"Christ","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071613091498600_R14","doi-asserted-by":"crossref","first-page":"8763","DOI":"10.1074\/jbc.271.15.8763","article-title":"Modulation of cytosolic protein kinase C and calcium ion activity by steroid hormones in rat distal colon.","volume":"271","author":"Doolan","year":"1996","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0303-7207(98)00020-3","article-title":"Rapid effects of corticosteroids on protein kinase C and intracellular calcium concentration in human distal colon.","volume":"138","author":"Doolan","year":"1998","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613091498600_R16","doi-asserted-by":"crossref","first-page":"C1673","DOI":"10.1152\/ajpcell.1997.273.5.C1673","article-title":"The mineralocorticoid aldosterone activates a proton conductance in cultured kidney cells","volume":"273","author":"Gekle","year":"1997","journal-title":"Am J Physiol"},{"key":"2020071613091498600_R17","doi-asserted-by":"crossref","first-page":"3410","DOI":"10.1210\/endo.138.8.5352","article-title":"Aldosterone rapidly represses protein kinase C activity in neonatal rat cardiomyocytes in vitro.","volume":"138","author":"Sato","year":"1997","journal-title":"Endocrinology"},{"key":"2020071613091498600_R18","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0304-3940(00)01457-9","article-title":"Vitamin E decreases valproic acid induced neural tube defects in mice.","volume":"292","author":"Al Deeb","year":"2000","journal-title":"Neurosci Lett"},{"key":"2020071613091498600_R19","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.2460\/ajvr.2000.61.1438","article-title":"Effect of dietary supplements containing antioxidants on attenuation of muscle damage in exercising sled dogs.","volume":"61","author":"Piercy","year":"2000","journal-title":"Am J Vet Res"},{"key":"2020071613091498600_R20","doi-asserted-by":"crossref","first-page":"11114","DOI":"10.1073\/pnas.191369098","article-title":"Opposing cardioprotective actions and parallel hypertrophic effects of \u03b4PKC and \u03b5PKC.","volume":"98","author":"Chen","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613091498600_R21","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1085\/jgp.94.3.539","article-title":"[Na] and [K] dependence of the Na\/K pump current-voltage relationship in guinea pig ventricular myocytes.","volume":"94","author":"Nakao","year":"1989","journal-title":"J Gen Physiol"},{"key":"2020071613091498600_R22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1172\/JCI115555","article-title":"Correlates of aldosterone-induced increases in Cai\n2+ is the second messenger fro stimulation of apical membrane conductance.","volume":"89","author":"Petzel","year":"1992","journal-title":"J Clin Invest"},{"key":"2020071613091498600_R23","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1006\/bbrc.1994.2484","article-title":"Rapid effects of aldosterone on free intracellular calcium in vascular smooth muscle and endothelial cells: subcellular localization of calcium elevations by single cell imaging.","volume":"204","author":"Wehling","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071613091498600_R24","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1161\/01.RES.76.6.973","article-title":"Nongenomic effects of aldosterone on intracellular Ca2+ in vascular smooth muscle cells.","volume":"76","author":"Wehling","year":"1995","journal-title":"Circ Res"},{"key":"2020071613091498600_R25","doi-asserted-by":"crossref","first-page":"H2658","DOI":"10.1152\/ajpheart.2000.279.6.H2658","article-title":"Evidence for functional role of \u03b5PKC isozyme in the regulation of cardiac Ca2+ channels","volume":"279","author":"Hu","year":"2000","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2020071613091498600_R26","doi-asserted-by":"crossref","first-page":"30945","DOI":"10.1074\/jbc.272.49.30945","article-title":"A selective \u03b5-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death.","volume":"272","author":"Gray","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R27","doi-asserted-by":"crossref","first-page":"24180","DOI":"10.1074\/jbc.270.41.24180","article-title":"C2 region-derived peptides inhibit translocation and function of \u03b2 protein kinase C in vivo.","volume":"270","author":"Ron","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R28","doi-asserted-by":"crossref","first-page":"12798","DOI":"10.1073\/pnas.96.22.12798","article-title":"Sustained in vivo cardiac protection by a rationally designed peptide that causes \u03b5 protein kinase C translocation.","volume":"96","author":"Dorn II","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613091498600_R29","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/0003-9861(91)90039-L","article-title":"Alpha-tocopherol (vitamin E) regulates vascular smooth muscle cell proliferation and protein kinase C activity.","volume":"286","author":"Boscoboinik","year":"1991","journal-title":"Arch Biochem Biophys"},{"key":"2020071613091498600_R30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1085\/jgp.104.2.197","article-title":"Partial reactions of the Na, K-ATPase: determination of rate constants.","volume":"104","author":"Heyse","year":"1994","journal-title":"J Gen Physiol"},{"key":"2020071613091498600_R31","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1074\/jbc.271.5.2470","article-title":"An effect of voltage on binding of Na+ at the cytoplasmic surface of the Na+-K+ pump.","volume":"271","author":"Or","year":"1996","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R32","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/BF00196828","article-title":"Investigation of ion binding to the cytoplasmic binding sites of the Na, K-pump.","volume":"23","author":"Schulz","year":"1995","journal-title":"Eur Biophys J"},{"key":"2020071613091498600_R33","first-page":"H1680","article-title":"Dietary cholesterol affects Na+-K+ pump function in rabbit cardiac myocytes","volume":"272","author":"Gray","year":"1997","journal-title":"Am J Physiol"},{"key":"2020071613091498600_R34","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1085\/jgp.94.3.511","article-title":"Steady-state current-voltage relationship of the Na\/K pump in guinea pig ventricular myocytes.","volume":"94","author":"Gadsby","year":"1989","journal-title":"J Gen Physiol"},{"key":"2020071613091498600_R35","doi-asserted-by":"crossref","first-page":"C461","DOI":"10.1152\/ajpcell.1999.277.3.C461","article-title":"Angiotensin regulates selectivity of the Na+-K+ pump for intracellular Na+","volume":"277","author":"Buhagiar","year":"1999","journal-title":"Am J Physiol"},{"key":"2020071613091498600_R36","first-page":"804","article-title":"Cyclosporine and FK506 differentially inhibit the sarcolemmal Na+-K+ pump.","volume":"297","author":"Mardini","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"key":"2020071613091498600_R37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0039-128X(01)00176-3","article-title":"Nongenomic effects of aldosterone: cellular aspects and clinical implications.","volume":"67","author":"Lo\u0308sel","year":"2002","journal-title":"Steroids"},{"key":"2020071613091498600_R38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1161\/01.CIR.92.2.175","article-title":"Prerequisite for cardiac aldosterone action. Mineralocorticoid receptor and 11\u03b2-hydroxysteroid dehydrogenase in the human heart.","volume":"92","author":"Lombes","year":"1995","journal-title":"Circulation"},{"key":"2020071613091498600_R39","first-page":"F863","article-title":"Effects of okadaic acid, calyculin A, and PDBu on state of phosphorylation of rat renal Na+-K+-ATPase","volume":"275","author":"Li","year":"1998","journal-title":"Am J Physiol"},{"key":"2020071613091498600_R40","doi-asserted-by":"crossref","first-page":"8814","DOI":"10.1074\/jbc.273.15.8814","article-title":"Phosphorylation of the catalyic \u03b1-subunit constitutes a triggering signal for Na+, K+-ATPase endocytosis.","volume":"273","author":"Chibalin","year":"1998","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R41","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1074\/jbc.274.4.1920","article-title":"Dopamine-induced endocytosis of Na+, K+-ATPase is initiated by phosphorylation of Ser-18 in the rat \u03b1 subunit and is responsible for the decreased activity in epithelial cells.","volume":"274","author":"Chibalin","year":"1999","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/S0014-5793(99)00851-0","article-title":"Mutations of Ser-23 of the \u03b11 subunit of the rat Na+\/K+-ATPase to negatively charged amino acid residues mimic the functional effect of PKC-mediated phosphorylation.","volume":"455","author":"Vasilets","year":"1999","journal-title":"FEBS Lett"},{"key":"2020071613091498600_R43","doi-asserted-by":"crossref","first-page":"15069","DOI":"10.1074\/jbc.272.24.15069","article-title":"Activation of the avian erythrocyte Na-K-Cl cotransport protein by cell shrinkage, cAMP, fluoride and calyculin-A involves phosphorylation at common sites.","volume":"272","author":"Lytle","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071613091498600_R44","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/cvr\/26.7.671","article-title":"Reactive and reparative myocardial fibrosis in arterial hypertension in the rat.","volume":"26","author":"Brilla","year":"1992","journal-title":"Cardiovasc Res"},{"key":"2020071613091498600_R45","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1161\/01.HYP.31.5.1083","article-title":"Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth muscle cells.","volume":"31","author":"Gu","year":"1998","journal-title":"Hypertension"},{"key":"2020071613091498600_R46","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1006\/jmcc.1999.0993","article-title":"Na+ influx via Na+\/H+ exchange activates protein kinase C isozymes \u03b4 and \u03b5 in cultured neonatal rat cardiac myocytes.","volume":"31","author":"Hayasaki-Kajiwara","year":"1999","journal-title":"J Mol Cell Cardiol"},{"key":"2020071613091498600_R47","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1161\/01.RES.86.12.1218","article-title":"Transgenic overexpression of constitutively active protein kinase C\u03b5 causes concentric cardiac hypertrophy.","volume":"86","author":"Takeishi","year":"2000","journal-title":"Circ Res"},{"key":"2020071613091498600_R48","first-page":"H1679","article-title":"PKC\u03b5 modulates NF-\u03baB and AP-1 via mitogen-activated protein kinases in adult rabbit cardiomyocytes","volume":"279","author":"Li","year":"2000","journal-title":"Am J Physiol"},{"key":"2020071613091498600_R49","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0303-7207(00)00258-6","article-title":"Tissue-specific corticosteroidogenesis in the rat.","volume":"165","author":"Rudolph","year":"2000","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613091498600_R50","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1210\/jcem.86.11.7925","article-title":"Cardiac steroidogenesis in the normal and failing heart.","volume":"86","author":"Young","year":"2001","journal-title":"J Endocrinol Metab"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/2\/773\/9023521\/endo0773.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/145\/2\/773\/9023521\/endo0773.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,16]],"date-time":"2020-07-16T23:09:05Z","timestamp":1594940945000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/145\/2\/773\/2500422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,2,1]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2004,2,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2003-1137","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,2,1]]}}}