Importance of Gradients in Membrane Properties and Electrical Coupling in Sinoatrial Node Pacing

Inada, Shin; Zhang, Henggui; Tellez, James O.; Shibata, Nitaro; Nakazawa, Kimitaka; Kamiya, Kaichiro; Kodama, Itsuo; Mitsui, Kazuyuki; Dobrzynski, Halina; Boyett, Mark R.; Honjo, Haruo

doi:10.1371/journal.pone.0094565

Cited by 42 publications

(43 citation statements)

References 33 publications

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“…A more interesting model is obtained if we abandon the one dimensional restriction of the series, for instance, when six or seven SA cells are attached to a series of A cells as shown in figure 7. This models contradict the claim of Inada et al [11] that suggest that a gradient in both electrical coupling and cell type is necessary for the SAN to drive the atrial muscle. The left hand side plot in figure 7 shows one of seven SA cells (the first) connected in a series with atrial cells, with same conductance g SAA = g AA =6nS.…”

Section: Atrial and Sinoatrial Cell Modelscontrasting

confidence: 83%

“…One dimensional models (series models) require only one tridiagonal matrix instead of sum of matrices as the model in [34]. In many models the transition between SA center and atrial zone is achieved with only one cell connected in one extreme with a SA cell, and in the other extreme connected to A cells; for instance in Inada et al model [13], one SA cell is connected with three series of 50 A cells each. Here is where this models are misleading.…”

Section: Discussionmentioning

confidence: 99%

“…Series models. In [11] the authors modeled the inter-phase in a series of 200 cells, the first 50 SA, where there is a gradient in the conductance of the Ionic currents inside the cells and also a gradient in the the membrane capacitance of SA Kurata et al cell model (see references within [11]). In that model there is also a gradient in the conductance between SA cells varying from g SA = 20 nS to 3999.8 nS, this last value, as the authors mention, exceed by far experimental values.…”

Section: Atrial and Sinoatrial Cell Modelsmentioning

confidence: 99%

“…In that model there is also a gradient in the conductance between SA cells varying from g SA = 20 nS to 3999.8 nS, this last value, as the authors 4/13 mention, exceed by far experimental values. In [13] Atrial cells are modeled with Lindblad et al [16] with g A = 4000 nS (neither observed experimentally). In that 1D model the inter-phase is attained by one SA cell (the 50th cell in a line) connected to three branches of 50 A cells each.…”

Section: Series Modelsmentioning

confidence: 99%

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Cell-to-Cell Modeling of the Interface Between Atrial and Sinoatrial Anisotropic Heterogeneous Nets

Lopez

Castellanos

Godı́nez³

2016

Preprint

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Abstract. The transition between Sinoatrial cells and Atrial cells in the Heart is not fully understood. Here we focus in cell-to-cell mathematical models involving typical Sinoatrial cells and Atrial cells connected with experimentally observed conductance values exclusively. We are interested mainly in the geometry of the microstructure of the conduction paths in the Sinoatrial Node. We show with some models that appropriate source-sink relationships between Atrial and Sinoatrial cells may occur according to certain geometric arrangements. Inter-phase between Atrial and Sinoatrial cellsIt has been observed in different species that going from the center of the sinoatrial node (SAN) in the heart toward the atrium, there is a transitional zone of cells having morphological and electrophysiological properties in-between to that of typical sinoatrial (SA) and atrial (A) cells [16]. The transitional cells have an aspect intermediate between that of typical nodal cells and that of the common atrial cells. Typical nodal cells have poor development of the contractile system and is assumed in general that they do not contract, moreover the existence of connexin43 is undetectable in the SA node center (see [3] and references therein), but posses automaticity in firing its action potential. On the contrary, atrial cells do contract themselves, but they require of an stimulus in order to contract, and they contain mainly connexin-43. This characteristics are included in the cells models used in this paper. A whole range of intermediate cells have been reported, but more important to the models in this paper, cells with one end connected to SA cells and the other end with A cells have been found [16]. The basic structure conforming the cytoarchitecture of this groups of cells consists of interdigitations of nodal and atrial bundles forming histological connections between nodal and atrial myocytes at regular distances [18].In [29] the authors, introduce a model of strands of atrial cells penetrating the SA node observed in the Pig. The model was constructed with 101 × 101 atrial and SA cells modeled with Oxsoft HEART V4.5. The lattice so constructed has a center of SA cells forming a circle of 30 cells of radius with twelve atrial interdigitations positioned at 30 deg intervals, where interdigitations are defined as sets of atrial cells at least ten cells distant from the node centre, and which are subtended by an angle of 15 deg. In that paper SA to SA conductance is g SA = 10 nS and the A to A conductance g A , varies from 10 nS to 250 nS.

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Section: Atrial and Sinoatrial Cell Modelscontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Atrial and Sinoatrial Cell Modelsmentioning

confidence: 99%

Section: Series Modelsmentioning

confidence: 99%

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Cell-to-Cell Modeling of the Interface Between Atrial and Sinoatrial Anisotropic Heterogeneous Nets

Lopez

Castellanos

Godı́nez³

2016

Preprint

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“…(Maltsev and Lakatta, 2012;DiFrancesco and Noble, 2012;Lakatta and Maltsev, 2012) The sinus node also has limited connectivity with the atrial myocardium so this electrical signal can start in a single myocyte or a few cells and gradually increase in size until it is sufficient to capture the atrial myocardium. (Fedorov, Schuessler et al 2009;Inada, Zhang et al 2014)…”

Section: Sinus Node Dysfunctionmentioning

confidence: 99%

Current state of the art for cardiac arrhythmia gene therapy

Donahue

2017

Pharmacology & Therapeutics

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Cardiac arrhythmias are a leading cause of morbidity and mortality. Currently available therapeutic options lack sufficient efficacy and safety. Gene therapy has been proposed for treatment of cardiac arrhythmias. This review will discuss the current state of development for arrhythmia gene therapy. So far, all published studies are short-term, proof-of-concept animal studies. Potential replacement of cardiac pacemakers has been shown for combination gene therapy using the HCN2 gene and either the gene for adenylate cyclase, the skeletal muscle isoform of the sodium channel, or a dominant negative mutant of the potassium channel responsible for resting membrane potential. Atrial fibrillation has been prevented by gene transfer of either a dominant negative mutant of a repolarizing potassium channel, a gap junction, or an siRNA directed against caspase 3. Inherited arrhythmia syndromes have been corrected by replacement of the causative genes. Post-infarct ventricular tachycardia has been reduced by gene therapy with the skeletal muscle sodium channel and connexins and eliminated with the dominant negative mutant of the potassium channel responsible for resting membrane potential. These ideas show considerable promise. Long-term efficacy and safety studies are required to see if they can become viable therapies.

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Parallel simulation of the synchronization of heterogeneous cells in the sinoatrial node

Mata¹,

Alonso²,

Garza

et al. 2019

Concurrency and Computation

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The cells of the sinoatrial node (SAN) are self-excitable entities that show a coupled electrical pattern that consists of the synchronized activation of action potentials that determine the heart rate. To accurately describe the behavior of cell membrane proteins, theoretical biophysicists have devoted themselves to the study of the electrical activity of individual cells, which involves solving a large number of coupled differential equations. This computational limitation makes the modeling of a large number of cells unattainable, since the intracellular distribution of Ca 2+ must be considered and this fact increases in grand extent the number of differential equations involved. In this work, we explore different parallel architectures (using OpenMP, MPI, and CUDA libraries) to show advances in the computational modeling and simulation of the SAN using a multicellular array in which the cells are endowed of heterogeneous conductances and are electrically coupled, considering a variable connectivity among them.

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Importance of Gradients in Membrane Properties and Electrical Coupling in Sinoatrial Node Pacing

Cited by 42 publications

References 33 publications

Cell-to-Cell Modeling of the Interface Between Atrial and Sinoatrial Anisotropic Heterogeneous Nets

Cell-to-Cell Modeling of the Interface Between Atrial and Sinoatrial Anisotropic Heterogeneous Nets

Current state of the art for cardiac arrhythmia gene therapy

Parallel simulation of the synchronization of heterogeneous cells in the sinoatrial node

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