title: Spatiotemporal dynamics of calcium-driven cardiac alternans.
abstract: We investigate the dynamics of spatially discordant alternans (SDA) driven by an instability of intracellular calcium cycling using both amplitude equations [P. S. Skardal, A. Karma, and J. G. Restrepo, Phys. Rev. Lett. 108, 108103 (2012)] and ionic model simulations. We focus on the common case where the bidirectional coupling of intracellular calcium concentration and membrane voltage dynamics produces calcium and voltage alternans that are temporally in phase. We find that, close to the alternans bifurcation, SDA is manifested as a smooth wavy modulation of the amplitudes of both repolarization and calcium transient (CaT) alternans, similarly to the well-studied case of voltage-driven alternans. In contrast, further away from the bifurcation, the amplitude of CaT alternans jumps discontinuously at the nodes separating out-of-phase regions, while the amplitude of repolarization alternans remains smooth. We identify universal dynamical features of SDA pattern formation and evolution in the presence of those jumps. We show that node motion of discontinuous SDA patterns is strongly hysteretic even in homogeneous tissue due to the novel phenomenon of "unidirectional pinning": node movement can only be induced towards, but not away from, the pacing site in response to a change of pacing rate or physiological parameter. In addition, we show that the wavelength of discontinuous SDA patterns scales linearly with the conduction velocity restitution length scale, in contrast to the wavelength of smooth patterns that scales sublinearly with this length scale. Those results are also shown to be robust against cell-to-cell fluctuations due to the property that unidirectional node motion collapses multiple jumps accumulating in nodal regions into a single jump. Amplitude equation predictions are in good overall agreement with ionic model simulations. Finally, we briefly discuss physiological implications of our findings. In particular, we suggest that due to the tendency of conduction blocks to form near nodes, the presence of unidirectional pinning makes calcium-driven alternans potentially more arrhythmogenic than voltage-driven alternans.
authors.affiliation: Departament d'Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, 43007 Tarragona, Spain and Department of Applied Mathematics, University of Colorado at Boulder, Colorado 80309, USA.
authors.forename: Per Sebastian
authors.initials: PS
authors.lastname: Skardal
authors.affiliation: Physics Department and Center for Interdisciplinary Research on Complex Systems, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Alain
authors.initials: A
authors.lastname: Karma
authors.affiliation: Department of Applied Mathematics, University of Colorado at Boulder, Colorado 80309, USA.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Restrepo
mesh_terms: D002118:Calcium / Q000378:metabolism*; D003198:Computer Simulation; D006321:Heart / Q000503:physiopathology*; D042541:Intracellular Space / Q000378:metabolism; D007477:Ions / Q000378:metabolism; D016014:Linear Models; D008564:Membrane Potentials / Q000502:physiology*; D008955:Models, Cardiovascular; D017711:Nonlinear Dynamics
chemical_list: D007477:Ions; D002118:Calcium