Spatial non-uniformity of excitation-contraction coupling can enhance arrhythmogenic-delayed afterdepolarizations in rat cardiac muscle

Masahito Miura, Yuji Wakayama, Hideaki Endoh, Makoto Nakano, Yoshinao Sugai, Masanori Hirose, Henk E.D.J. Ter Keurs, Hiroaki Shimokawa

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Aims: We examined whether non-uniform muscle contraction affects delayed afterdepolarizations (DADs) by dissociating Ca2+ from myofilaments within the border zone (BZ) between contracting and stretched regions. Methods and results: Force, sarcomere length (SL), membrane potential, and [Ca 2+]i dynamics were measured in 31 ventricular trabeculae from rat hearts. Non-uniform muscle contraction was produced by exposing a restricted region of muscle to a jet of solution containing 20 mmol/L 2,3-butanedione monoxime (BDM). DADs were induced by 7.5 s-2 Hz stimulus trains at an SL of 2.0 μm (24°C, [Ca2+]o 2.0 mmol/L). The BDM jet enhanced DADs (n = 6, P < 0.05) and aftercontractions (n = 6, P < 0.05) with or without 100 μmol/L streptomycin and occasionally elicited an action potential. A stretch pulse from an SL of 2.0 μm to 2.1 or 2.2 μm during the last stimulated twitch of the trains accelerated Ca2+ waves in proportion to the increment of force by the stretch (P < 0.01) with or without streptomycin. In the presence of 1 mmol/L caffeine, rapid shortening of the muscle after the stretch pulse increased [Ca2+]i within the BZ, whose amplitude correlated with the increment of force by the stretch (n = 15, P < 0.01). Conclusion: These results suggest that non-uniform muscle contraction can enhance DADs by dissociating Ca2+ from myofilaments within the BZ and thereby cause triggered arrhythmias.

Original languageEnglish
Pages (from-to)55-61
Number of pages7
JournalCardiovascular Research
Volume80
Issue number1
DOIs
Publication statusPublished - 2008 Oct 1

Keywords

  • Ca waves
  • Delayed afterdepolarizations
  • Non-uniformity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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