Abstract
We introduce the Difference-Current Integral (DCI) method as a tool for quantitative assessment of contributions by individual model components to dynamic responses at the system’s level. Using a detailed model of cardiac electrophysiology and mechanics, we assess the relative effects of mechano-sensitive ion channels and intracellular calcium handling to stretch-induced changes in action potential (AP) characteristics. DCI supports the hypothesis that some of the experimentally observed variability in cardiac AP responses to mechanical stimulation may be caused by differences in activation of underlying mechanisms, rather than solely species or technical differences. In particular, the model suggests that systems with a pronounced reverse mode Na+-Ca2+ exchange during the AP will respond to mechanical interventions that affect primarily cellular Ca2+ handling with AP shortening, whereas a predominant contribution of mechano-sensitive ion channels, in particular cation non-selective ones, may cause late AP prolongation and cross-over of repolarisation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Kohl, P., Nesbitt, A.D., Cooper, P.J., Lei, M.: Sudden Cardiac Death by Commotio Cordis: Role of Mechano-Electric Feedback. Cardiovasc. Res. 50 (2001) 280–289
Kohl, P., Hunter, P., Noble, D.: Stretch-Induced Changes in Heart Rate and Rhythm: Clinical Observations, Experiments and Mathematical Models. Prog. Biophys. Mol. Biol. 71.1 (1999) 91–138
Solovyova, O., Vikulova, N., Katsnelson, L.B., Markhasin, V.S., Noble, P.J., Garny, A.F., Kohl, P., Noble, D.: Mechanical Interaction of Heterogeneous Cardiac Muscle Segments in Silico: Effects on Ca2+ Handling and Action Potential. Int. J. Bifurcation and Chaos (2003) in press
Noble, D., Varghese, A., Kohl, P., Noble, P.: Improved Guinea-Pig Ventricular Cell Model Incorporating a Diadic Space, Ikr and Iks, and Length-and Tension-Dependent Processes. Can. J. Cardiol. 14.1 (1998) 123–134
Solovyova, O., Katsnelson, L., Guriev, S., Nikitina, L., Protsenko, Y., Routkevitch, S., Markhasin, V.: Mechanical Inhomogeneity of Myocardium Studied in Parallel and Serial Cardiac Muscle Duplexes: Experiments and Models. Chaos, Solitons & Fractals 13.8 (2002) 1685–1711
Gordon, A.M., Regnier, M., Homsher, E.: Skeletal and Cardiac Muscle Contractile Activation: Tropomyosin “Rocks and Rolls”. News Physiol. Sci. 16 (2001) 49–55
Katsnelson, L.B., Markhasin, V.S.: Mathematical Modeling of Relations between the Kinetics of Free Intracellular Calcium and Mechanical Function of Myocardium. J. Mol. Cell. Cardiol. 28.3 (1996) 475–486
Hongo, K., White, E., Le Guennec, J.Y., Orchard, C.H.: Changes in [Ca2+]I, [Na+]I and Ca2+ Current in Isolated Rat Ventricular Myocytes Following an Increase in Cell Length. J. Physiol. 491.3 (1996) 609–619
Kohl, P., Sachs, F.: Mechano-Electric Feedback in Cardiac Cells. Phil. Trans. R. Soc. Lond. A 359 (2001) 1173–1185
Kohl, P., Day, K., Noble, D.: Cellular Mechanisms of Cardiac Mechano-Electric Feedback in a Mathematical Model. Can. J. Cardiol. 14.1 (1998) 111–119
Lab, M.J., Allen, D.G., Orchard, C.H.: The Effects of Shortening on Myoplasmic Calcium Concentration and on the Action Potential in Mammalian Ventricular Muscle. Circ. Res. 55.6 (1984) 825–829
White, E., Le Guennec, J.Y., Nigretto, J.M., Gannier, F., Argibay, J.A., Garnier, D.: The Effects of Increasing Cell Length on Auxotonic Contractions; Membrane Potential and Intracellular Calcium Transients in Single Guinea-Pig Ventricular Myocytes. Exp. Physiol. 78.1 (1993) 65–78
Hansen, D.E.: Mechanoelectrical Feedback Effects of Altering Preload, Afterload, and Ventricular Shortening. Am. J. Physiol. 264 (1993) H423–H432
Kamkin, A., Kiseleva, I., Isenberg, G.: Stretch-Activated Currents in Ventricular Myocytes: Amplitude and Arrhythmogenic Effects Increase with Hypertrophy. Cardiovasc. Res. 48.3 (2000) 409–420
Zabel, M., Koller, B.S., Sachs, F., Franz, M.R.: Stretch-Induced Voltage Changes in the Isolated Beating Heart: Importance of the Timing of Stretch and Implications for Stretch-Activated Ion Channels. Cardiovasc. Res. 32 (1996) 120–130
Belus, A., White, E.: Streptomycin and Intracellular Calcium Modulate the Response of Single Guinea-Pig Ventricular Myocytes to Axial Stretch. J. Physiol. 546.2 (2003) 501–509
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Solovyova, O., Vikulova, N., Markhasin, V.S., Kohl, P. (2003). A Novel Method for Quantifying the Contribution of Different Intracellular Mechanisms to Mechanically Induced Changes in Action Potential Characteristics. In: Magnin, I.E., Montagnat, J., Clarysse, P., Nenonen, J., Katila, T. (eds) Functional Imaging and Modeling of the Heart. FIMH 2003. Lecture Notes in Computer Science, vol 2674. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-44883-7_2
Download citation
DOI: https://doi.org/10.1007/3-540-44883-7_2
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-40262-6
Online ISBN: 978-3-540-44883-9
eBook Packages: Springer Book Archive