Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists. Kirchhefer, U.; Jones, L. R.; Begrow, F.; Boknik, P.; Hein, L.; Lohse, M. J.; Riemann, B.; Schmitz, W.; Stypmann, J.; and Neumann, J. Cardiovasc Res, 62(1):122-34, Apr 1, 2004. 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.
Transgenic triadin 1 overexpression alters SR Ca2+ handling and leads to a blunted contractile response to beta-adrenergic agonists [link]Paper  abstract   bibtex   
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 = {http://www.bibsonomy.org/bibtex/20381c2cd35b2b0940bc5fc5bceba1734/pharmawuerz},
  endnotereftype = {Journal Article},
  interhash = {71b8cd23cd2a8659a6784f6879496ef0},
  intrahash = {0381c2cd35b2b0940bc5fc5bceba1734},
  issn = {0008-6363 (Print) 0008-6363 (Linking)},
  journal = {Cardiovasc Res},
  keywords = {Calcium/analysis/*metabolism Contraction/*drug Phosphorylation beta-Agonists/*pharmacology Reticulum/*metabolism Sarcoplasmic Electrophysiology Confocal Transgenic Adrenergic Echocardiography, effects Animals Proteins/genetics/*metabolism Carrier Myocardial Microscopy, Electrocardiography Mice Muscle Doppler Caffeine},
  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 = {2010-12-14T18:12:16.000+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
}
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