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(Circulation Research. 2004;95:1135.)
© 2004 American Heart Association, Inc.

Editorials

The Ongoing Journey to Understand Heart Function Through Integrative Modeling

Raimond L. Winslow, Joseph L. Greenstein

From The Center for Cardiovascular Bioinformatics and Modeling and The Whitaker Biomedical Engineering Institute, Johns Hopkins University School of Medicine and Whiting School of Engineering, Md.

Correspondence to Raimond L. Winslow, Rm 201B Clark Hall, The Johns Hopkins University, 3400 N Charles St, Baltimore, MD 21218. E-mail rwinslow@bme.jhu.edu

See related article, pages 1216–1224

Key Words: hear function • modeling • cardiac electrophysiology

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Cardiac electrophysiology is a field with a rich history of integrative modeling that has been coupled closely with design and interpretation of experiments. The first models of the cardiac action potential (AP)¹ were developed shortly after the Hodgkin–Huxley model of the squid AP and were formulated to explain the experimental observation that, unlike neuronal APs, cardiac APs exhibit a long duration plateau phase. Over the subsequent 20 years, refinement of these models to incorporate emerging experimental data on properties of voltage-gated membrane currents, transport and exchange processes regulating intracellular ion concentrations, and mechanisms of calcium (Ca²⁺)-induced Ca²⁺-release (CICR) led to the first integrative model of the cardiac AP, the DiFrancesco–Noble model.² This landmark model of the Purkinje fiber AP provided the electrophysiological community a mathematical framework on which to build, thus stimulating development of a broad range of integrative cardiac myocyte models. These now include models of canine, guinea pig, human and rabbit ventricular myocytes,^3–8 sinoatrial node cells (for review, see Wilders et al⁹) and atrial myocytes.^10,11

Recent research efforts have been directed at extending the range of biophysical and biochemical mechanisms included in these models to enhance their explanatory and predictive capabilities. Important areas of research include: (1) use of single-channel and whole cell current data, in combination with knowledge of channel protein structure, to develop continuous time Markov chain models of voltage-gated channels and membrane transporters^12,13; (2) development and integration of mechanistic models of the CICR process^12,14,15; (3) modeling of force generation¹⁶; . . . [Full Text of this Article]

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Proarrhythmic Consequences of a KCNQ1 AKAP-Binding Domain Mutation: Computational Models of Whole Cells and Heterogeneous Tissue

Jeffrey J. Saucerman, Sarah N. Healy, Mary E. Belik, Jose L. Puglisi, and Andrew D. McCulloch
Circ. Res. 2004 95: 1216-1224. [Abstract] [Full Text] [PDF]

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