Role of sarcomere mechanics and Ca2+ overload in Ca2+ waves and arrhythmias in rat cardiac muscle

Henk E.D.J. Ter Keurs, Yuji Wakayama, Yoshinao Sugai, Guy Price, Yutaka Kagaya, Penelope A. Boyden, Masahito Miura, Bruno D.M. Stuyvers

Research output: Chapter in Book/Report/Conference proceedingConference contribution

38 Citations (Scopus)

Abstract

Ca2+ release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca2+ load and the cytosolic Ca 2+ level. Arrhythmogenic Ca2+ waves underlying triggered propagated contractions arise from Ca2+ overloaded regions near damaged areas in the cardiac muscle. Ca2+ waves can also be induced in undamaged muscle, in regions with nonuniform excitation-contraction (EC) coupling by the cycle of stretch and release in the border zone between the damaged and intact regions. We hypothesize that rapid shortening of sarcomeres in the border zone during relaxation causes Ca2+ release from troponin C (TnC) on thin filaments and initiates Ca2+ waves. Elimination of this shortening will inhibit the initiation of Ca2+ waves, while SR Ca2+ overload will enhance the waves. Force, sarcomere length (SL), and [Ca2+]i were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca2+] 10 mM (HC), or HC containing BDM, was used to weaken a 300 μm long muscle segment. Trains of electrical stimuli were used to induce Ca2+ waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca2+ waves (Vprop) were studied. Sarcomere shortening was uniform prior to activation. HC induced spontaneous diastolic sarcomere contractions in the jet region and attenuated twitch sarcomere shortening; HC+ butanedione monoxime (BDM) caused stretch only in the jet region. Stimulus trains induced Ca2+ waves, which started inside the HC jet region during twitch relaxation. Ca2+ waves started in the border zone of the BDM jet. The initial local [Ca2+]i rise of the waves by HC was twice that by BDM. The waves propagated at a Vprop of 2.0 ± 0.2 mm/sec. Arrhythmias occurred frequently in trabeculae following exposure to the HC jet. Stretch early during relaxation, which reduced sarcomere shortening in the weakened regions, substantially decreased force of the TPC (FTPC) and delayed Ca2+ waves, and reduced V prop commensurate with the reduction FTPC. These results are consistent with the hypothesis that Ca2+ release from the myofilaments initiates arrhythmogenic propagating Ca2+ release. Prevention of sarcomere shortening, by itself, did not inhibit Ca2+ wave generation. SR Ca2+ overload potentiated initiation and propagation of Ca2+ waves.

Original languageEnglish
Title of host publicationInteractive and Integrative Cardiology
PublisherBlackwell Publishing Inc.
Pages248-267
Number of pages20
ISBN (Print)1573316512, 9781573316514
DOIs
Publication statusPublished - 2006 Oct

Publication series

NameAnnals of the New York Academy of Sciences
Volume1080
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Arrhythmogenic
  • Ca overload
  • Ca waves
  • SR
  • Shortening

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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