title: Altered function in atrium of transgenic mice overexpressing triadin 1.
abstract: Triadin 1 is a protein in the cardiac junctional sarcoplasmic reticulum (SR) that interacts with the ryanodine receptor, junctin, and calsequestrin, proteins that are important for Ca(2+) release. To better understand the role of triadin 1 in SR-Ca(2+) release, we studied the time-dependent expression of SR proteins and contractility in atria of 3-, 6-, and 18-wk-old transgenic mice overexpressing canine cardiac triadin 1 under control of the alpha-myosin heavy chain (MHC) promoter. Three-week-old transgenic atria exhibited mild hypertrophy. Finally, atrial weight was increased by 110% in 18-wk-old transgenic mice. Triadin 1 overexpression was accompanied by time-dependent changes in the protein expression of the ryanodine receptor, junctin, and cardiac/slow-twitch muscle SR Ca(2+)-ATPase isoform. Force of contraction was already decreased in 3-wk-old transgenic atria. The application of caffeine led to a positive inotropic effect in transgenic atria of 3-wk-old mice. Rest pauses resulted in an increased potentiation of force of contraction after restimulation in 3- and 6-wk-old mice and a reduced potentiation of force of contraction in 18-wk-old transgenic mice. Hence, triadin 1 overexpression triggered time-dependent alterations in SR protein expression, Ca(2+) homeostasis, and contractility, indicating for the first time an inhibitory function of triadin 1 on SR-Ca(2+) release in vivo.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität, 48149 Münster, Germany. kirchhef@uni-muenster.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Kirchhefer
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Kobayashi
authors.forename: Larry R
authors.initials: LR
authors.lastname: Jones
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schmitz
authors.forename: Joachim
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000367:Age Factors; D000818:Animals; D016275:Atrial Function; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D004558:Electric Stimulation; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D006325:Heart Atria / Q000473:pathology; D006706:Homeostasis / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D006899:Mixed Function Oxygenases; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban
chemical_list: D002110:Caffeine; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D006899:Mixed Function Oxygenases; D009124:Muscle Proteins; D010726:Phosphodiesterase Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C498269:TRDN protein, human; C498270:Trdn protein, mouse; C070048:triadin; C498841:Asph protein, mouse