HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 563/1/73    most recent jphysiol.2004.080457v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Winslow, R. L Articles by Greenstein, J. L Search for Related Content PubMed PubMed Citation Articles by Winslow, R. L Articles by Greenstein, J. L Related Collections Review articles

¹ Center for Cardiovascular Bioinformatics and Modelling, The Johns Hopkins University School of Medicine and Whiting School of Engineering, Baltimore, MD, USA

There has been significant progress towards the development of highly integrative computational models of the cardiac myocyte over the past decade. Models now incorporate descriptions of voltage-gated ionic currents and membrane transporters, mechanisms of calcium-induced calcium release and intracellular calcium cycling, mitochondrial ATP production and its coupling to energy-requiring membrane transport processes and mechanisms of force generation. There is an extensive literature documenting both the reconstructive and predictive abilities of these models and there is no question that an interplay between quantitative modelling and experimental investigation has become a central component of modern cardiovascular research. As data regarding the cardiovascular proteome in both health and disease emerge, integrative models of the myocyte are becoming useful tools for interpreting the functional significance of changes in protein expression and post-translational modifications (PTMs). Data of particular importance include information on: (a) changes of expressed protein level, (b) changes of protein PTMs, (c) protein localization, and (d) protein–protein interactions, as it is often possible to incorporate and interpret the functional significance of such findings using computational models. We provide two examples of how models may be used in this fashion. In the first example, we show how information on altered expression of the sarcoplasmic reticulum Ca²⁺-ATPase, when interpreted through the use of a computational model, has provided key insights into fundamental mechanisms regulating cardiac action potential duration. In the second example, we show how information on the effects of phosphorylation of L-type Ca²⁺ channels, when interpreted through the use of a model, provides insights on how this post-translational modification alters the properties of excitation–contraction coupling and risk for arrhythmia.

(Received 1 December 2004; accepted after revision 15 December 2004; first published online 20 December 2004)
Corresponding author R. L. Winslow: Rm. 201B Clark Hall, 3400 N. Charles St, Baltimore, MD 21218, USA. Email: rwinslow{at}bme.jhu.edu

This article has been cited by other articles:

				T. D. Vo and B. O. Palsson Building the power house: recent advances in mitochondrial studies through proteomics and systems biology Am J Physiol Cell Physiol, January 1, 2007; 292(1): C164 - C177. [Abstract] [Full Text] [PDF]

				S. P. Patel and D. L. Campbell Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms J. Physiol., November 15, 2005; 569(1): 7 - 39. [Abstract] [Full Text] [PDF]