Title | Feedback-control induced pattern formation in cardiac myocytes: a mathematical modeling study. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Gaeta SA, Krogh-Madsen T, Christini DJ |
Journal | J Theor Biol |
Volume | 266 |
Issue | 3 |
Pagination | 408-18 |
Date Published | 2010 Oct 07 |
ISSN | 1095-8541 |
Keywords | Action Potentials, Algorithms, Animals, Arrhythmias, Cardiac, Calcium, Computer Simulation, Feedback, Physiological, Humans, Intracellular Space, Models, Cardiovascular, Myocytes, Cardiac, Sarcomeres, Sodium-Calcium Exchanger |
Abstract | Cardiac alternans is a dangerous rhythm disturbance of the heart, in which rapid stimulation elicits a beat-to-beat alternation in the action potential duration (APD) and calcium (Ca) transient amplitude of individual myocytes. Recently, "subcellular alternans", in which the Ca transients of adjacent regions within individual myocytes alternate out-of-phase, has been observed. A previous theoretical study suggested that subcellular alternans may result during static pacing from a Turing-type symmetry breaking instability, but this was only predicted in a subset of cardiac myocytes (with negative Ca to voltage (Ca-->V(m)) coupling) and has never been directly verified experimentally. A recent experimental study, however, showed that subcellular alternans is dynamically induced in the remaining subset of myocytes during pacing with a simple feedback control algorithm ("alternans control"). Here we show that alternans control pacing changes the effective coupling between the APD and the Ca transient (V(m)-->Ca coupling), such that subcellular alternans is predicted to occur by a Turing instability in cells with positive Ca-->V(m) coupling. In addition to strengthening the understanding of the proposed mechanism for subcellular alternans formation, this work (in concert with previous theoretical and experimental results) illuminates subcellular alternans as a striking example of a biological Turing instability in which the diffusing morphogens can be clearly identified. |
DOI | 10.1016/j.jtbi.2010.06.041 |
Alternate Journal | J. Theor. Biol. |
PubMed ID | 20620154 |
PubMed Central ID | PMC2927785 |
Grant List | 1F30HL095324-01 / HL / NHLBI NIH HHS / United States F30 HL095324 / HL / NHLBI NIH HHS / United States GM07739 / GM / NIGMS NIH HHS / United States R01 HL094620 / HL / NHLBI NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States 1R01HL094620 / HL / NHLBI NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:10pm