Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte
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 mechanis...
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| Format: | Article |
| Language: | en_US |
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Institute of Electrical and Electronics Engineers
2010
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| Online Access: | http://hdl.handle.net/1721.1/52424 |
| _version_ | 1826208948351401984 |
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| author | Armoundas, Antonis A. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Armoundas, Antonis A. |
| author_sort | Armoundas, Antonis A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:15:17Z |
| format | Article |
| id | mit-1721.1/52424 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:15:17Z |
| publishDate | 2010 |
| publisher | Institute of Electrical and Electronics Engineers |
| record_format | dspace |
| spelling | mit-1721.1/524242022-10-01T20:07:15Z Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte Armoundas, Antonis A. Harvard University--MIT Division of Health Sciences and Technology Armoundas, Antonis A. Armoundas, Antonis A. sarcoplasmic reticulum (SR) ryanodine receptor (RyR) myocyte cellular alternans model 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. Scientist Development (Grant 0635127N) American Heart Association awards (Beginning Grant-in-Aid 0365304U) 2010-03-09T18:41:34Z 2010-03-09T18:41:34Z 2009-08 2009-02 Article http://purl.org/eprint/type/JournalArticle 0018-9294 INSPEC Accession Number: 10828626 http://hdl.handle.net/1721.1/52424 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 19497812 en_US http://dx.doi.org/10.1109/tbme.2009.2023671 IEEE Transactions on Bio-medical Engineering 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. application/pdf Institute of Electrical and Electronics Engineers IEEE |
| spellingShingle | sarcoplasmic reticulum (SR) ryanodine receptor (RyR) myocyte cellular alternans model Armoundas, Antonis A. Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title | Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title_full | Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title_fullStr | Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title_full_unstemmed | Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title_short | Discordant Calcium Transient and Action Potential Alternans in a Canine Left-Ventricular Myocyte |
| title_sort | discordant calcium transient and action potential alternans in a canine left ventricular myocyte |
| topic | sarcoplasmic reticulum (SR) ryanodine receptor (RyR) myocyte cellular alternans model |
| url | http://hdl.handle.net/1721.1/52424 |
| work_keys_str_mv | AT armoundasantonisa discordantcalciumtransientandactionpotentialalternansinacanineleftventricularmyocyte |