Experimentally calibrated population of models predicts and explains intersubject variability in cardiac cellular electrophysiology
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- Oliver J. Britton
- Department of Computer Science, University of Oxford, Oxford OX1 3QD, United Kingdom;
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- Alfonso Bueno-Orovio
- Oxford Centre for Collaborative Applied Mathematics, Mathematical Institute, University of Oxford, Oxford OX1 3LB, United Kingdom; and
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- Karel Van Ammel
- Translational Sciences, Safety Pharmacology Research, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium
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- Hua Rong Lu
- Translational Sciences, Safety Pharmacology Research, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium
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- Rob Towart
- Translational Sciences, Safety Pharmacology Research, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium
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- David J. Gallacher
- Translational Sciences, Safety Pharmacology Research, Janssen Research and Development, Janssen Pharmaceutica NV, B-2340 Beerse, Belgium
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- Blanca Rodriguez
- Department of Computer Science, University of Oxford, Oxford OX1 3QD, United Kingdom;
説明
<jats:title>Significance</jats:title> <jats:p>Causes of intersubject variability in electrophysiological activity are unknown. We describe a methodology to unravel the ionic determinants of variability exhibited in experimental cardiac action potential recordings, based on the construction and calibration of populations of models. We show that 213 of 10,000 candidate models are consistent with the control experimental dataset. Ionic properties across the model population cover a wide range of values, and particular combinations of ionic properties determine shape, amplitude, and rate dependence of specific action potentials. Finally, we demonstrate that the calibrated model population quantitatively predicts effects caused by four concentrations of a potassium channel blocker.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 110 (23), E2098-, 2013-05-20
Proceedings of the National Academy of Sciences