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Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 16, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn162
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Spatial Non-uniformity of Excitation-Contraction Coupling Can Enhance Arrhythmogenic Delayed Afterdepolarizations in Rat Cardiac Muscle

Masahito Miura1, Yuji Wakayama2, Hideaki Endoh2, Makoto Nakano2, Yoshinao Sugai2, Masanori Hirose2, Henk EDJ ter Keurs3 and Hiroaki Shimokawa2

1 Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
2 Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
3 Department of Medicine, University of Calgary, Calgary T2N4M1, Canada

Address for correspondence and reprints: Masahito Miura M.D., Ph.D. Department of Clinical Physiology, Health Science Tohoku University Graduate School of Medicine 2-1 Seiryo-machi, Aoba-ku Sendai, Miyagi 980-8574, Japan Tel: 81-22-717-7920 Fax: 81-22-717-7920 E-mail: mmiura{at}cardio.med.tohoku.ac.jp

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: Force, sarcomere length (SL), membrane potential, and [Ca2+]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 a SL of 2.0 µm (24°C, [Ca2+]o=2.0 mmol/L).

Results: 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 a 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.

KEYWORDS Ca2+ waves; non-uniformity; delayed afterdepolarizations

Time for primary review: 29 days


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