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Role of Sarcomere Mechanics and Ca 2+ Overload in Ca 2+ Waves and Arrhythmias in Rat Cardiac Muscle
Author(s) -
TER KEURS HENK E.D.J.,
WAKAYAMA YUJI,
SUGAI YOSHINAO,
PRICE GUY,
KAGAYA YUTAKA,
BOYDEN PENELOPE A.,
MIURA MASAHITO,
STUYVERS BRUNO D.M.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1380.020
Subject(s) - sarcomere , physics , cardiac muscle , wave mechanics , medicine , classical mechanics , myocyte
Ca 2+ release from the sarcoplasmic reticulum (SR) depends on the sarcoplasmic reticulum (SR) Ca 2+ load and the cytosolic Ca 2+ level. Arrhythmogenic Ca 2+ waves underlying triggered propagated contractions arise from Ca 2+ overloaded regions near damaged areas in the cardiac muscle. Ca 2+ 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 Ca 2+ release from troponin C (TnC) on thin filaments and initiates Ca 2+ waves. Elimination of this shortening will inhibit the initiation of Ca 2+ waves, while SR Ca 2+ overload will enhance the waves. Force, sarcomere length (SL), and [Ca 2+ ] i were measured and muscle length was controlled. A small jet of Hepes solution with an extracellular [Ca 2+ ] 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 Ca 2+ waves. The effects of small exponential stretches on triggered propagatory contraction (TPC) amplitude and propagation velocity of Ca 2+ waves (V prop ) 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 Ca 2+ waves, which started inside the HC jet region during twitch relaxation. Ca 2+ waves started in the border zone of the BDM jet. The initial local [Ca 2+ ] i rise of the waves by HC was twice that by BDM. The waves propagated at a V prop 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 (F TPC ) and delayed Ca 2+ waves, and reduced V prop commensurate with the reduction F TPC . These results are consistent with the hypothesis that Ca 2+ release from the myofilaments initiates arrhythmogenic propagating Ca 2+ release. Prevention of sarcomere shortening, by itself, did not inhibit Ca 2+ wave generation. SR Ca 2+ overload potentiated initiation and propagation of Ca 2+ waves.