Abstract Expression and activity of cardiac Na + /Ca 2+ exchanger (NCX1) are altered in many disease states. We engineered mice in which the phosphomimetic phospholemman S68E mutant (inhibits NCX1 but not Na + -K + -ATPase) was constitutively overexpressed in a cardiac-specific manner (conS68E). At 4–6 wk, conS68E mice exhibited severe bradycardia, ventricular arrhythmias, increased left ventricular (LV) mass, decreased cardiac output (CO), and ∼50% mortality compared with wild-type (WT) littermates. Protein levels of NCX1, calsequestrin, ryanodine receptor, and α 1 - and α 2 -subunits of Na + -K + -ATPase were similar, but sarco(endo)plasmic reticulum Ca 2+ -ATPase was lower, whereas L-type Ca 2+ channels were higher in conS68E hearts. Resting membrane potential and action potential amplitude were similar, but action potential duration was dramatically prolonged in conS68E myocytes. Diastolic intracellular Ca 2+ ((Ca 2+ ) i ) was higher, (Ca 2+ ) i transient and maximal contraction amplitudes were lower, and half-time of (Ca 2+ ) i transient decline was longer in conS68E myocytes. Intracellular Na + reached maximum within 3 min after isoproterenol addition, followed by decline in WT but not in conS68E myocytes. Na + /Ca 2+ exchange, L-type Ca 2+ , Na + -K + -ATPase, and depolarization-activated K + currents were decreased in conS68E myocytes. At 22 wk, bradycardia and increased LV mass persisted in conS68E survivors. Despite comparable baseline CO, conS68E survivors at 22 wk exhibited decreased chronotropic, inotropic, and lusitropic responses to isoproterenol. We conclude that constitutive overexpression of S68E mutant was detrimental, both in terms of depressed cardiac function and increased arrhythmogenesis. intracellular Ca 2+ and Na + regulation in vivo catheterization β-adrenergic responsiveness FXYD proteins Copyright © 2012 the American Physiological Society « Previous | Next Article » Table of Contents This Article Published online before print November 2011 , doi: 10.​1152/​ajpheart.​00733.​2011 AJP - Heart February 2012 vol. 302 no. 3 H770-H781 » Abstract Free Full Text Free to you Full Text (PDF) Free to you All Versions of this Article: ajpheart.00733.2011v1 302/3/H770 most recent Classifications Cardiac Excitation and Contraction Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Citing articles via Web of Science Google Scholar Articles by Song, J. Articles by Cheung, J. Y. PubMed PubMed citation Articles by Song, J. Articles by Cheung, J. Y. Related Content Load related web page information Current Issue February 2012, 302 (3) Alert me to new issues of AJP - Heart About the Journal Information for Authors Submit a Manuscript Ethical Policies AuthorChoice PubMed Central Policy Reprints and Permissions Advertising Press Copyright © 2012 the American Physiological Society Print ISSN: 0363-6135 Online ISSN: 1522-1539 var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-2924550-1"); pageTracker._trackPageview();

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