Altered function in atrium of transgenic mice overexpressing triadin 1

Am J Physiol Heart Circ Physiol. 2002 Oct;283(4):H1334-43. doi: 10.1152/ajpheart.00937.2001.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Atrial Function
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism
  • Calcium-Transporting ATPases / metabolism
  • Calsequestrin / genetics
  • Calsequestrin / metabolism
  • Cardiomegaly / genetics
  • Cardiomegaly / pathology
  • Cardiomegaly / physiopathology
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism*
  • Electric Stimulation
  • Gene Expression
  • Heart / physiology*
  • Heart Atria / pathology
  • Homeostasis / physiology
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins*
  • Mice
  • Mice, Transgenic
  • Mixed Function Oxygenases*
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism*
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Phenotype
  • Phosphodiesterase Inhibitors / pharmacology
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases


  • Calcium-Binding Proteins
  • Calsequestrin
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Muscle Proteins
  • Phosphodiesterase Inhibitors
  • Ryanodine Receptor Calcium Release Channel
  • TRDN protein, human
  • Trdn protein, mouse
  • phospholamban
  • triadin
  • Caffeine
  • Asph protein, mouse
  • Mixed Function Oxygenases
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcium