{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:29:35Z","timestamp":1792499375181,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2019,6,7]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>PKA (Protein Kinase A) is a major mediator of \u03b2-AR (\u03b2-adrenergic) regulation of cardiac function, but other mediators have also been suggested. Reduced PKA basal activity and activation are linked to cardiac diseases. However, how complete loss of PKA activity impacts on cardiac physiology and if it causes cardiac dysfunction have never been determined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objectives:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We set to determine how the heart adapts to the loss of cardiomyocyte PKA activity and if it elicits cardiac abnormalities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              (1) Cardiac PKA activity was almost completely inhibited by expressing a PKA inhibitor peptide in cardiomyocytes (cPKAi) in mice; (2) cPKAi reduced basal phosphorylation of 2 myofilament proteins (TnI [troponin I] and cardiac myosin binding protein C), and one longitudinal SR (sarcoplasmic reticulum) protein (PLB [phospholamban]) but not of the sarcolemmal proteins (Cav1.2 \u03b11c and PLM [phospholemman]), dyadic protein RyR2, and nuclear protein CREB (cAMP response element binding protein) at their PKA phosphorylation sites; (3) cPKAi increased the expression of CaMKII (Ca\n              <jats:sup>2+<\/jats:sup>\n              \/calmodulin-dependent kinase II), the Cav1.2 \u03b2 subunits and current, but decreased CaMKII phosphorylation and CaMKII-mediated phosphorylation of PLB and RyR2; (4) These changes resulted in significantly enhanced myofilament Ca\n              <jats:sup>2+<\/jats:sup>\n              sensitivity, prolonged contraction, slowed relaxation but increased myocyte Ca\n              <jats:sup>2+<\/jats:sup>\n              transient and contraction amplitudes; (5) Isoproterenol-induced PKA and CaMKII activation and their phosphorylation of proteins were prevented by cPKAi; (6) cPKAi abolished the increases of heart rate, and cardiac and myocyte contractility by a \u03b2-AR agonist (isoproterenol), showing an important role of PKA and a minimal role of PKA-independent \u03b2-AR signaling in acute cardiac regulation; (7) cPKAi mice have partial exercise capability probably by enhancing vascular constriction and ventricular filling during \u03b2-AR stimulation; and (8) cPKAi mice did not show any cardiac functional or structural abnormalities during the 1-year study period.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              PKA activity suppression induces a unique Ca\n              <jats:sup>2+<\/jats:sup>\n              handling phenotype, eliminates \u03b2-AR regulation of heart rates and cardiac contractility but does not cause cardiac abnormalities.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.118.313417","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T09:02:20Z","timestamp":1555318940000},"page":"1760-1777","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Cardiomyocyte PKA Ablation Enhances Basal Contractility While Eliminates Cardiac \u03b2-Adrenergic Response Without Adverse Effects on the Heart"],"prefix":"10.1161","volume":"124","author":[{"given":"Ying","family":"Zhang","sequence":"first","affiliation":[{"name":"Cardiology, Daping Hospital, Third Military Medical University, Chongqing (Y.Z., W.E.W., C. Zeng, L.Z.)"},{"name":"Endocrinology and Metabolism, The First Affiliated Hospital of Zhengzhou University (Y.Z.)"},{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei Eric","family":"Wang","sequence":"additional","affiliation":[{"name":"Cardiology, Daping Hospital, Third Military Medical University, Chongqing (Y.Z., W.E.W., C. Zeng, L.Z.)"},{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"},{"name":"The General Hospital of The PLA Rocket Force, Beijing, China (Y.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine, Fran\u00e7ois M. Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine (B.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"},{"name":"Pharmacology, Second Military Medical University, Shanghai (C.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"},{"name":"School of Agriculture and Biology, Shanghai Key Laboratory of Veterinary Biotechnology, Shanghai Jiao Tong University (X.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cardiovascular Research Center (Y.Z., W.E.W., X.Z., Y.L., C.L., X.A., X.Z., C.Z., M.T., C.S., S.R.H., X.C.), Temple University School of Medicine, Philadelphia, PA"},{"name":"Department of Ultrasound, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan (X.Z., M.X.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center for Translational Medicine (Y.T., W.Z.), Temple University School of Medicine, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiology, Daping Hospital, Third Military Medical University, Chongqing (Y.Z., W.E.W., C. 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