Comparisons of wave dynamics in Hodgkin-Huxley and Markov-state formalisms for the sodium (Na) channel in some mathematical models for human cardiac tissue

Mulimani, MK and Nayak, AR and Pandit, R (2020) Comparisons of wave dynamics in Hodgkin-Huxley and Markov-state formalisms for the sodium (Na) channel in some mathematical models for human cardiac tissue. In: Physical Review Research, 2 (3).

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Abstract

We compare and contrast the excitation properties of cardiac myocytes and cardiac tissue modeled by (a) a Hodgkin-Huxley-model (HHM) and (b) Markov-chain-model (MM) formalisms for the sodium (Na) ion channel. Specifically, we bring out the differences between HHM and MM formalisms, for both wild-type (WT) and mutant (MUT) models, for ion-channel kinetics, single-myocyte action potentials, and the spatiotemporal evolutions of spiral and scroll waves in different mathematical models of cardiac tissue. We show that the kinetic properties of Na ion channels are not the same for HHM and MM models; in particular, the range of values of the trans-membrane potential Vm, in which there is a significant window current, depends significantly on these models, so there are marked differences in the opening times of the Na ion channels, the maximal amplitude of the Na current, and the presence or absence of a late Na current. Furthermore, these changes lead to different excitation behaviors in cardiac tissue; specifically, two of the WT models show stable spiral waves, but the other one shows meandering and transiently breaking spiral waves. Our results are based on extensive direct numerical simulations of waves of electrical activation in these models, in two- A nd three-dimensional (2D and 3D) homogeneous simulation domains and also in domains with localized heterogeneities, either obstacles with randomly distributed inexcitable regions or mutant cells in a wild-type background. Our study brings out the sensitive dependence of spiral- A nd scroll-wave dynamics on these five models and the parameters that define them. We list desiderata for a good model for the Na wild-type ion channel; we use these desired properties to select one of the MM models that we study. © 2020 authors. Published by the American Physical Society.

Item Type:	Journal Article
Publication:	Physical Review Research
Publisher:	American Physical Society
Additional Information:	The copyright for this article belongs to American Physical Society
Keywords:	Electrophysiology; Heart; Ions; Markov chains; Sodium; Wavefronts, Electrical activation; Excitation properties; Hodgkin-Huxley models; Kinetic properties; Markov chain models; Randomly distributed; Simulation domain; Spatiotemporal evolution, Tissue
Department/Centre:	Division of Physical & Mathematical Sciences > Physics
Date Deposited:	28 Nov 2021 10:09
Last Modified:	28 Nov 2021 10:09
URI:	http://eprints.iisc.ac.in/id/eprint/70318

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