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PMID: 10866940 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A mathematical model of cardiocyte Ca(2+) dynamics with a novel representation of sarcoplasmic reticular Ca(2+) control.

Biophysical journal ·Vol. 79 ·No. 1 ·2000-07-00 ·Pages 94-115

Snyder SM, Palmer BM, Moore RL

Abstract

Cardiac contraction and relaxation dynamics result from a set of simultaneously interacting Ca(2+) regulatory mechanisms. In this study, cardiocyte Ca(2+) dynamics were modeled using a set of six differential equations that were based on theories, equations, and parameters described in previous studies. Among the unique features of the model was the inclusion of bidirectional modulatory interplay between the sarcoplasmic reticular Ca(2+) release channel (SRRC) and calsequestrin (CSQ) in the SR lumen, where CSQ acted as a dynamic rather than simple Ca(2+) buffer, and acted as a Ca(2+) sensor in the SR lumen as well. The inclusion of this control mechanism was central in overcoming a number of assumptions that would otherwise have to be made about SRRC kinetics, SR Ca(2+) release rates, and SR Ca(2+) release termination when the SR lumen is assumed to act as a simple, buffered Ca(2+) sink. The model was sufficient to reproduce a graded Ca(2+)-induced Ca(2+) release (CICR) response, CICR with high gain, and a system with reasonable stability. As constructed, the model successfully replicated the results of several previously published experiments that dealt with the Ca(2+) dependence of the SRRC (, J. Gen. Physiol. 85:247-289), the refractoriness of the SRRC (, Am. J. Physiol. 270:C148-C159), the SR Ca(2+) load dependence of SR Ca(2+) release (, Am. J. Physiol. 268:C1313-C1329;, J. Biol. Chem. 267:20850-20856), SR Ca(2+) leak (, J. Physiol. (Lond.). 474:463-471;, Biophys. J. 68:2015-2022), SR Ca(2+) load regulation by leak and uptake (, J. Gen. Physiol. 111:491-504), the effect of Ca(2+) trigger duration on SR Ca(2+) release (, Am. J. Physiol. 258:C944-C954), the apparent relationship that exists between sarcoplasmic and sarcoplasmic reticular calcium concentrations (, Biophys. J. 73:1524-1531), and a variety of contraction frequency-dependent alterations in sarcoplasmic [Ca(2+)] dynamics that are normally observed in the laboratory, including rest potentiation, a negative frequency-[Ca(2+)] relationship, and extrasystolic potentiation. Furthermore, under the condition of a simulated Ca(2+) overload, an alternans-like state was produced. In summary, the current model of cardiocyte Ca(2+) dynamics provides an integrated theoretical framework of fundamental cellular Ca(2+) regulatory processes that is sufficient to predict a broad array of observable experimental outcomes.

MeSH Terms
Animals Calcium/metabolism Calcium Channels/metabolism Calcium-Transporting ATPases/metabolism Cell Compartmentation/physiology Computer Simulation Cytosol/metabolism Ion Transport/physiology Models, Cardiovascular Muscle Contraction/physiology Myocardium/cytology,metabolism Predictive Value of Tests Rats Sarcolemma/metabolism Sarcoplasmic Reticulum/metabolism
Chemicals
Calcium Channels Calcium-Transporting ATPases Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Snyder S M
Department of Kinesiology and Applied Physiology, The University of Colorado Cardiovascular Institute (CUCVI), University of Colorado, Boulder, Colorado 80309-0354, USA.
Palmer B M
Moore R L
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1016/S0006-3495(00)76276-X
Published
2000-07-00
Pages
94-115
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1300918
Subset
IM
Grants
NIA NIH HHS · AG13987 · United States
NHLBI NIH HHS · HL40306 · United States
Corrections
CommentIn
PMID: 11203466
External Links
PubMed source DOI: 10.1016/S0006-3495(00)76276-X PMC Full Text View journal details
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