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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Animals
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Atrial Function
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Caffeine / pharmacology
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Calcium / metabolism
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Calcium-Transporting ATPases / metabolism
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Calsequestrin / genetics
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Calsequestrin / metabolism
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Cardiomegaly / genetics
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Cardiomegaly / pathology
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Cardiomegaly / physiopathology
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Electric Stimulation
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Gene Expression
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Heart / physiology*
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Heart Atria / pathology
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Homeostasis / physiology
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins*
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Mice
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Mice, Transgenic
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Mixed Function Oxygenases*
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Muscle Proteins / genetics*
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Muscle Proteins / metabolism*
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Myocardial Contraction / drug effects
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Myocardial Contraction / physiology
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Phenotype
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Phosphodiesterase Inhibitors / pharmacology
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Ryanodine Receptor Calcium Release Channel / genetics
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Ryanodine Receptor Calcium Release Channel / metabolism
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
Substances
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Calcium-Binding Proteins
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Calsequestrin
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Muscle Proteins
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Phosphodiesterase Inhibitors
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Ryanodine Receptor Calcium Release Channel
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TRDN protein, human
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Trdn protein, mouse
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phospholamban
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triadin
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Caffeine
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Asph protein, mouse
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Mixed Function Oxygenases
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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Calcium-Transporting ATPases
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Calcium