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PMID: 15465866 Published · ppublish English Comparative Study Evaluation Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A simplified local control model of calcium-induced calcium release in cardiac ventricular myocytes.

Biophysical journal ·Vol. 87 ·No. 6 ·2004-12-00 ·Pages 3723-36

Hinch R, Greenstein JL, Tanskanen AJ, Xu L, Winslow RL

Abstract

Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.

MeSH Terms
Animals Calcium/metabolism Calcium Channels, L-Type/physiology Calcium Signaling/physiology Cell Membrane/physiology Computer Simulation Humans Ion Channel Gating/physiology Membrane Potentials/physiology Models, Cardiovascular Myocardial Contraction/physiology Myocytes, Cardiac/physiology Ryanodine Receptor Calcium Release Channel/physiology Ventricular Function
Chemicals
Calcium Channels, L-Type Ryanodine Receptor Calcium Release Channel Calcium
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hinch R
Mathematical Institute, University of Oxford, Oxford, United Kingdom. [email protected]
Greenstein J L
Tanskanen A J
Xu L
Winslow R L
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1529/biophysj.104.049973
Email
[email protected]
Published
2004-12-00
Epub
2004-00-01
Pages
3723-36
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1304886
Subset
IM
Grants
NHLBI NIH HHS · R01 HL061711 · United States
NHLBI NIH HHS · R01 HL-60133 · United States
NHLBI NIH HHS · R01 HL072488 · United States
NHLBI NIH HHS · R01 HL-61711 · United States
NHLBI NIH HHS · R01 HL-72488 · United States
NHLBI NIH HHS · R01 HL060133 · United States
NHLBI NIH HHS · P50 HL-52307 · United States
NHLBI NIH HHS · N01 HV028180 · United States
External Links
PubMed source DOI: 10.1529/biophysj.104.049973 PMC Full Text View journal details
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