Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte
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Armoundas-2009-Discordant Calcium T.pdf
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Author(s)
Armoundas, Antonis A.
Date Issued
August 2009
Journal
IEEE Transactions on Bio-medical Engineering
Publisher
Institute of Electrical and Electronics Engineers
Citation
Armoundas, A.A. “Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte.” Biomedical Engineering, IEEE Transactions on 56.9 (2009): 2340-2344. © 2009 Institute of Electrical and Electronics Engineers
Version
Final published version
Abstract
Electrocardiographic alternans is known to predispose to increased susceptibility to life threatening arrhythmias and sudden cardiac death. While this decreased level of cardiac electrical stability is often due to the presence of discordant action potential (AP) alternans in the heart, the mechanism of discordant cardiac alternans remains unknown. This study presents a case report of cellular discordant cardiac alternans between AP and [Ca[superscript 2+]]i and employs a novel reverse engineering approach that applies a simultaneous AP and [Ca2[superscript 2+]]i clamp of experimentally obtained data to a left-ventricular canine myocyte model, to probe its underlying mechanism. The model results indicate that during alternans, the increased sarcoplasmic reticulum Ca[superscript 2+], triggers multiple ryanodine receptor (RyR) channel openings and delayed Ca[superscript 2+] release, which subsequently triggers an inward depolarizing current, a subthreshold early after-depolarization, and AP prolongation. The amplitude of [Ca[superscript 2+]]i plays a critical role in defining the concordant or discordant relationship between the [Ca[superscript 2+]]i and AP at the myocyte level. In conclusion, the results presented in this study support the idea that aberrant RyR openings on alternate beats are responsible for the [Ca[superscript 2+]]i alternan-type oscillations, which, in turn, give rise to an in- or out-of-phase relationship between [Ca[superscript 2+]]i and AP alternans.
Subjects
sarcoplasmic reticulum (SR)
ryanodine receptor (RyR)
myocyte
cellular alternans
model
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
http://dx.doi.org/10.1109/tbme.2009.2023671
