scholarly journals Ranolazine-Mediated Attenuation of Mechanoelectric Feedback in Atrial Myocyte Monolayers

2020 ◽  
Vol 11 ◽  
Author(s):  
Irene Del-Canto ◽  
Lidia Gómez-Cid ◽  
Ismael Hernández-Romero ◽  
María S. Guillem ◽  
María Eugenia Fernández-Santos ◽  
...  
Keyword(s):  
Mechanoelectric Feedback ◽  
Atrial Myocyte

scholarly journals Accelerating mono-domain cardiac electrophysiology simulations using OpenCL

2015 ◽  
Vol 1 (1) ◽  
pp. 413-417
Author(s):  
Eike M. Wülfers ◽  
Zhasur Zhamoliddinov ◽  
Olaf Dössel ◽  
Gunnar Seemann
Keyword(s):  
Cardiac Electrophysiology ◽  
Cardiac Tissue ◽  
Ionic Currents ◽  
Domain Model ◽  
Electrical Excitation ◽  
Simulation Domain ◽  
Speed Up ◽  
Cross Platform ◽  
Atrial Myocyte ◽  
Intel Xeon

AbstractUsing OpenCL, we developed a cross-platform software to compute electrical excitation conduction in cardiac tissue. OpenCL allowed the software to run parallelized and on different computing devices (e.g., CPUs and GPUs). We used the macroscopic mono-domain model for excitation conduction and an atrial myocyte model by Courtemanche et al. for ionic currents. On a CPU with 12 HyperThreading-enabled Intel Xeon 2.7 GHz cores, we achieved a speed-up of simulations by a factor of 1.6 against existing software that uses OpenMPI. On two high-end AMD FirePro D700 GPUs the OpenCL software ran 2.4 times faster than the OpenMPI implementation. The more nodes the discretized simulation domain contained, the higher speed-ups were achieved.

scholarly journals Ca2+/calmodulin-dependent kinase II-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling, and excitability: a mathematical modeling study

2017 ◽  
Vol 313 (6) ◽  
pp. H1227-H1239 ◽  
Author(s):  
Birce Onal ◽  
Daniel Gratz ◽  
Thomas J. Hund
Keyword(s):  
Protein Kinase ◽  
Computational Model ◽  
Ryanodine Receptor ◽  
The United States ◽  
Atrial Myocytes ◽  
Open Probability ◽  
Dependent Protein Kinase ◽  
Protein Kinase Ii ◽  
Dependent Protein ◽  
Atrial Myocyte

Atrial fibrillation (AF) affects more than three million people per year in the United States and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the regulation of persistent “late” Na+ current ( INa,L) has been identified. Although INa,L inhibition is emerging as a potential antiarrhythmic strategy in patients with AF, little is known about the mechanism linking INa,L to atrial arrhythmogenesis. A computational approach was used to test the hypothesis that increased CaMKII-activated INa,L in atrial myocytes disrupts Ca2+ homeostasis, promoting arrhythmogenic afterdepolarizations. Dynamic CaMKII activity and regulation of multiple downstream targets [ INa,L, L-type Ca2+ current, phospholamban, and the ryanodine receptor sarcoplasmic reticulum Ca2+-release channel (RyR2)] were incorporated into an existing well-validated computational model of the human atrial action potential. Model simulations showed that constitutive CaMKII-dependent phosphorylation of Nav1.5 and the subsequent increase in INa,L effectively disrupt intracellular atrial myocyte ion homeostasis and CaMKII signaling. Specifically, increased INa,L promotes intracellular Ca2+ overload via forward-mode Na+/Ca2+ exchange activity, which greatly increases RyR2 open probability beyond that observed for CaMKII-dependent phosphorylation of RyR2 alone. Increased INa,L promotes atrial myocyte repolarization defects (afterdepolarizations and alternans) in the setting of acute β-adrenergic stimulation. We anticipate that our modeling efforts will help identify new mechanisms for atrial NaV1.5 regulation with direct relevance for human AF. NEW & NOTEWORTHY Here, we present a novel computational model to study the effects of late Na+ current ( INa,L) in human atrial myocytes. Simulations predict that INa,L promotes intracellular accumulation of Ca2+, with subsequent dysregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling and ryanodine receptor 2-mediated Ca2+ release. Although INa,L plays a small role in regulating atrial myocyte excitability at baseline, CaMKII-dependent enhancement of the current promoted arrhythmogenic dynamics. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/camkii-dependent-regulation-of-atrial-late-sodium-current-and-excitability/ .

scholarly journals Computational modeling of the electromechanical response of a ventricular fiber affected by eccentric hypertrophy

2017 ◽  
Vol 8 (1) ◽  
pp. 185-209
Author(s):  
Fabrizio Del Bianco ◽  
Piero Colli Franzone ◽  
Simone Scacchi ◽  
Lorenzo Fassina
Keyword(s):  
Coupled Model ◽  
Electrical Current ◽  
Mechanoelectric Feedback ◽  
Isotonic Contraction ◽  
Strongly Coupled ◽  
One Dimensional ◽  
Electromechanical Responses ◽  
Eccentric Hypertrophy ◽  
Dimensional Finite Element ◽  
Simulation Results

AbstractThe aim of this work is to study the effects of eccentric hypertrophy on the electromechanics of a single myocardial ventricular fiber by means of a one-dimensional finite-element strongly-coupled model. The electrical current ow model is written in the reference configuration and it is characterized by two geometric feedbacks, i.e. the conduction and convection ones, and by the mechanoelectric feedback due to stretchactivated channels. First, the influence of such feedbacks is investigated for both a healthy and a hypertrophic fiber in case of isometric simulations. No relevant discrepancies are found when disregarding one or more feedbacks for both fibers. Then, all feedbacks are taken into account while studying the electromechanical responses of fibers. The results from isometric tests do not point out any notable difference between the healthy and hypertrophic fibers as regards the action potential duration and conduction velocity. The length-tension relationships show increased stretches and reduced peak values for tension instead. The tension-velocity relationships derived from afterloaded isotonic and quick- release tests depict higher values of contraction velocity at smaller afterloads. Moreover, higher maximum shortenings are achieved during the isotonic contraction. In conclusion, our simulation results are innovative in predicting the electromechanical behavior of eccentric hypertrophic fibers.

Effects of JTV-519 on stretch-induced manifestations of mechanoelectric feedback

2016 ◽  
Vol 43 (11) ◽  
pp. 1062-1070 ◽  
Author(s):  
Irene del Canto ◽  
Luis Such-Miquel ◽  
Laia Brines ◽  
Carlos Soler ◽  
Manuel Zarzoso ◽  
...  
Keyword(s):  
Mechanoelectric Feedback

593 Evidence of mechanoelectric feedback in the atria of patients with atrioventricular nodal reentrant tachycardia

EP Europace ◽  
2005 ◽  
Vol 7 (Supplement_1) ◽  
pp. 133-133
Author(s):  
E.M. Kanoupakis ◽  
E.G. Manios ◽  
H.E. Mavrakis ◽  
I.K. Karalis ◽  
D.A. Arfanakis ◽  
...  
Keyword(s):  
Atrioventricular Nodal Reentrant Tachycardia ◽  
Reentrant Tachycardia ◽  
Mechanoelectric Feedback

Acetylcholine activates a glibenclamide-sensitive K+ current in cat atrial myocytes

1995 ◽  
Vol 268 (3) ◽  
pp. H1322-H1334 ◽  
Author(s):  
Y. G. Wang ◽  
S. L. Lipsius
Keyword(s):  
Muscarinic Receptor ◽  
Preceding Paper ◽  
Kinase C ◽  
M2 Muscarinic Receptor ◽  
Cell Recording ◽  
K Current ◽  
Receptor Block ◽  
Atrial Myocyte ◽  
M1 Muscarinic ◽  
K Currents

The preceding paper [Y. G. Wang and S. L. Lipsius, Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H1313–H1321, 1995.] showed that when an atrial myocyte is treated with two consecutive exposures to acetylcholine (ACh) separated by a recovery interval, the second ACh exposure elicits a larger increase in K+ conductance than the first ACh exposure. In the present study a nystatin-perforated patch whole cell recording method was used to determine the mechanisms underlying the potentiating effect of ACh on ACh-induced K+ currents and the nature of the potentiated K+ current. The K+ current potentiated by the second ACh exposure was selectively abolished by 1) M1 muscarinic receptor block by 0.1 microM pirenzepine, 2) depletion of sarcoplasmic reticulum (SR) Ca2+ stores by 1 microM ryanodine or 10 mM caffeine, 3) intracellular dialysis with 10 mM ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), 4) omitting external Ca2+, 5) 50% external Na+, 6) inhibition of protein kinase C by 0.01 microM staurosporine or 0.1 microM calphostin C, or 7) inhibition of ATP-sensitive K+ channels with 10 microM glibenclamide (Glib). AFDX-116 (100 microM), an M2 muscarinic receptor antagonist, selectively abolished the conventional ACh-activated K+ current and revealed an ACh-activated Glib-sensitive K+ current. In addition, with K+ conductances blocked and zero external Ca2+, 10 microM ACh induced a small nonselective inward current carried by Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Regional electromechanical alternans in anesthetized pig hearts: modulation by mechanoelectric feedback

1994 ◽  
Vol 267 (5) ◽  
pp. H1726-H1735 ◽  
Author(s):  
C. F. Murphy ◽  
M. J. Lab ◽  
S. M. Horner ◽  
D. J. Dick ◽  
F. G. Harrison
Keyword(s):  
Left Ventricle ◽  
Action Potential ◽  
Monophasic Action Potential ◽  
Mechanical Activity ◽  
Strain Gauges ◽  
Atrial Pacing ◽  
Mechanoelectric Feedback ◽  
Pulsus Alternans ◽  
Electrical Alternans ◽  
Intact Heart

Electrical and mechanical alternans have often been found to coexist. However, the factors controlling their interdependence are not known. In this study we measure regional electrical and mechanical activity during mechanical alternans to investigate this relationship. Mechanical alternans was induced by rapid atrial pacing in 18 anesthetized, open-chest pigs. Regional segmental contraction and monophasic action potential were measured in three areas of left ventricle using epicardial tripodal strain gauges and suction electrodes. Electrical alternans always accompanied pulsus alternans. The phase of electrical alternans was not related to any measure of regional mechanical activity but did show a constant discordant relation to peak ventricular pressure. This suggested that mechanically dependent changes in action potential duration (mechanoelectric feedback) may be important in modulation electrical alternans. In support of this, pulsus alternans simulated by clamping the proximal aorta on alternate beats was associated with electrical alternans comparable to that produced with rapid atrial pacing. Mechanoelectric feedback modulates regional electrophysiology in the intact heart and may be important in the generation of electrical alternans.

scholarly journals A Mathematical Model of the Mouse Atrial Myocyte With Inter-Atrial Electrophysiological Heterogeneity

2020 ◽  
Vol 11 ◽  
Author(s):  
Henggui Zhang ◽  
Shanzhuo Zhang ◽  
Wei Wang ◽  
Kuanquan Wang ◽  
Weijian Shen
Keyword(s):  
Mathematical Model ◽  
Atrial Myocyte
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