%0 Journal Article %1 Kirchhefer2004 %A Kirchhefer, U. %A Jones, L. R. %A Begrow, F. %A Boknik, P. %A Hein, L. %A Lohse, M. J. %A Riemann, B. %A Schmitz, W. %A Stypmann, J. %A Neumann, J. %D 2004 %J Cardiovasc Res %K Adrenergic Animals Caffeine Calcium/analysis/*metabolism Carrier Confocal Contraction/*drug Doppler Echocardiography, Electrocardiography Electrophysiology Mice Microscopy, Muscle Myocardial Phosphorylation Proteins/genetics/*metabolism Reticulum/*metabolism Sarcoplasmic Transgenic beta-Agonists/*pharmacology effects %N 1 %P 122-34 %T Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15023559 %V 62 %X OBJECTIVE: Ca2+ release from the cardiac junctional sarcoplasmic reticulum (SR) is regulated by a complex of proteins, including the ryanodine receptor (RyR), calsequestrin (CSQ), junctin (JCN), and triadin 1 (TRD). Moreover, triadin 1 appears to anchor calsequestrin to the ryanodine receptor. METHODS: To determine whether triadin 1 overexpression alters excitation-contraction coupling, we examined the effects of cardiac-specific overexpression of triadin 1 on SR Ca2+ handling and contractility in transgenic (TG) compared to wild-type (WT) mice. RESULTS: The overexpression of triadin 1 was associated with an enhanced SR Ca2+ load, reflected by a 22% higher amplitude of caffeine-induced Ca2+ transients. The decline of Ca2+ transients during caffeine exposure was prolonged by 57%. The detection of resting spontaneous SR Ca2+ release events (Ca2+ sparks) revealed an increased amplitude (by 16%), decline (by 47%), and width (by 47%) in TG. This was associated with a redistribution of Ca2+ spark amplitudes from one population to two populations. Measurement of cardiac function by echocardiography and left ventricular (LV) catheterization revealed a decreased cardiac contractility in vivo. The impaired response to beta-adrenergic receptor (beta-AR) stimulation in TG hearts was associated with an increased protein expression of beta-AR kinase 1. In addition, the increase of the L-type Ca2+ peak current and the increase of phospholamban (PLB) phosphorylation at Thr17 were reduced under beta-AR stimulation. CONCLUSION: Taken together, our data suggest that triadin 1 overexpression results in a complex modulation of SR Ca2+ handling, which may contribute, at least in part, to the depressed basal contractility and the blunted response to beta-adrenergic agonists in TG mice.

@article{Kirchhefer2004, abstract = {OBJECTIVE: Ca2+ release from the cardiac junctional sarcoplasmic reticulum (SR) is regulated by a complex of proteins, including the ryanodine receptor (RyR), calsequestrin (CSQ), junctin (JCN), and triadin 1 (TRD). Moreover, triadin 1 appears to anchor calsequestrin to the ryanodine receptor. METHODS: To determine whether triadin 1 overexpression alters excitation-contraction coupling, we examined the effects of cardiac-specific overexpression of triadin 1 on SR Ca2+ handling and contractility in transgenic (TG) compared to wild-type (WT) mice. RESULTS: The overexpression of triadin 1 was associated with an enhanced SR Ca2+ load, reflected by a 22% higher amplitude of caffeine-induced Ca2+ transients. The decline of Ca2+ transients during caffeine exposure was prolonged by 57%. The detection of resting spontaneous SR Ca2+ release events (Ca2+ sparks) revealed an increased amplitude (by 16%), decline (by 47%), and width (by 47%) in TG. This was associated with a redistribution of Ca2+ spark amplitudes from one population to two populations. Measurement of cardiac function by echocardiography and left ventricular (LV) catheterization revealed a decreased cardiac contractility in vivo. The impaired response to beta-adrenergic receptor (beta-AR) stimulation in TG hearts was associated with an increased protein expression of beta-AR kinase 1. In addition, the increase of the L-type Ca2+ peak current and the increase of phospholamban (PLB) phosphorylation at Thr17 were reduced under beta-AR stimulation. CONCLUSION: Taken together, our data suggest that triadin 1 overexpression results in a complex modulation of SR Ca2+ handling, which may contribute, at least in part, to the depressed basal contractility and the blunted response to beta-adrenergic agonists in TG mice.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Kirchhefer, U. and Jones, L. R. and Begrow, F. and Boknik, P. and Hein, L. and Lohse, M. J. and Riemann, B. and Schmitz, W. and Stypmann, J. and Neumann, J.}, biburl = {https://www.bibsonomy.org/bibtex/20381c2cd35b2b0940bc5fc5bceba1734/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {71b8cd23cd2a8659a6784f6879496ef0}, intrahash = {0381c2cd35b2b0940bc5fc5bceba1734}, issn = {0008-6363 (Print) 0008-6363 (Linking)}, journal = {Cardiovasc Res}, keywords = {Adrenergic Animals Caffeine Calcium/analysis/*metabolism Carrier Confocal Contraction/*drug Doppler Echocardiography, Electrocardiography Electrophysiology Mice Microscopy, Muscle Myocardial Phosphorylation Proteins/genetics/*metabolism Reticulum/*metabolism Sarcoplasmic Transgenic beta-Agonists/*pharmacology effects}, month = {Apr 1}, note = {Kirchhefer, Uwe Jones, Larry R Begrow, Frank Boknik, Peter Hein, Lutz Lohse, Martin J Riemann, Burkhard Schmitz, Wilhelm Stypmann, Jorg Neumann, Joachim HL-28556/HL/NHLBI NIH HHS/United States Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Netherlands Cardiovascular research Cardiovasc Res. 2004 Apr 1;62(1):122-34.}, number = 1, pages = {122-34}, shorttitle = {Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists}, timestamp = {2010-12-14T18:21:25.000+0100}, title = {Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15023559}, volume = 62, year = 2004 }