Effects of stochastic channel gating and distribution on the cardiac action potential

Lemay, Mathieu; Lange, Enno de; Kučera, Jan

doi:10.1016/j.jtbi.2011.04.019

Cited by 41 publications

(60 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lemay et al published that stochastic gating of certain ion channels (ion channels responsible for L-type calcium current, late sodium current, slow component of the delayed rectifier potassium current) contribute primarily to the action potential repolarization variability of single cardiac cells [13]. Our results underline the importance of stochastic channel gating in the development of SBVR, too.…”

Section: The Short Term Beat-to-beat Variability Of Cardiac Action Posupporting

confidence: 66%

“…To the best of our knowledge the mechanism of SBVR is multifactorial including: stochastic ion-channel gating [12][13][14], pharmacological interventions influencing ion channels that operate during the action potential plateau and repolarization [2], periodic calcium release of sarcoplasmic reticulum [15], and electrotonic interactions among the cardiac cells can influence it [10,12].…”

Section: The Short Term Beat-to-beat Variability Of Cardiac Action Pomentioning

confidence: 99%

See 1 more Smart Citation

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Magyar

Bányász

Szentandrássy

et al. 2014

CPD

View full text Add to dashboard Cite

The short-term beat-to-beat variability of cardiac action potential duration (SBVR) occurs as a random alteration of the ventricular repolarization duration. SBVR has been suggested to be more predictive of the development of lethal arrhythmias than the action potential prolongation or QT prolongation of ECG alone. The mechanism underlying SBVR is not completely understood but it is known that SBVR depends on stochastic ion channel gating, intracellular calcium handling and intercellular coupling.Coupling of single cardiomyocytes significantly decreases the beat-to-beat changes in action potential duration (APD) due to the electrotonic current flow between neighboring cells. The magnitude of this electrotonic current depends on the intercellular gap junction resistance. Reduced gap junction resistance causes greater electrotonic current flow between cells, and reduces SBVR.Myocardial ischaemia (MI) is known to affect gap junction channel protein expression and function. MI increases gap junction resistance that leads to slow conduction, APD and refractory period dispersion, and an increase in SBVR. Ultimately, development of reentry arrhythmias and fibrillation are associated post-MI. Antiarrhythmic drugs have proarrhythmic side effects requiring alternative approaches. A novel idea is to target gap junction channels. Specifically, the use of gap junction channel enhancers and inhibitors may help to reveal the precise role of gap junctions in the development of arrhythmias. Since cell-to-cell coupling is represented in SBVR, this parameter can be used to monitor the degree of coupling of myocardium.

show abstract

Section: The Short Term Beat-to-beat Variability Of Cardiac Action Posupporting

confidence: 66%

Section: The Short Term Beat-to-beat Variability Of Cardiac Action Pomentioning

confidence: 99%

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Magyar

Bányász

Szentandrássy

et al. 2014

CPD

View full text Add to dashboard Cite

show abstract

“…By this approach, we have documented that, together with depressed diastolic performance, reduction in Kv K + and L‐type Ca 2+ current densities, protracted electrical recovery, and enhanced temporal dispersion of repolarization are initial functional defects of the myocardium dictated by diabetes. The process linking reduced ionic currents with the enhanced beat‐to‐beat variability of electrical recovery of the diabetic heart may involve complex multiscale mechanisms, from ion channels to the whole organ 22, 23, 54, 55. The reduced repolarizing effect of Kv currents has attenuated the repolarization reserve of diabetic myocytes, potentially unmasking fluctuations of ionic currents caused by stochastic behavior of ion channel gating, normally concealed by K + efflux.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Meo

Meste

Signore

et al. 2016

JAHA

View full text Add to dashboard Cite

BackgroundDiabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization.Methods and ResultsDiabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K+ and L‐type Ca2+ currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes.ConclusionsReductions in the repolarizing K+ currents may contribute to electrical disturbances of the diabetic heart.

show abstract

“…The use of combined experimental and computational approaches can be a useful tool for such investigations [82]. In [83], [84] and [85] it was hypothesized that fluctuations in ionic currents caused by stochasticity in ion channel behavior contribute to variability in cardiac repolarization, particularly under pathological conditions. Also it was postulated that electrotonic interactions through intercellular coupling act to mitigate spatiotemporal variability in repolarization dynamics in tissue, as compared to isolated cells.…”

Section: ) Qt Adaptation To Hr Changesmentioning

confidence: 99%

“…Also it was postulated that electrotonic interactions through intercellular coupling act to mitigate spatiotemporal variability in repolarization dynamics in tissue, as compared to isolated cells. The approaches taken in [83], [84] and [85] combine experimental and computational investigations in human, guinea pig and dog. Multiscale stochastic models of ventricular electrophysiology are used, bridging ion channel numbers to whole organ behavior.…”

Section: ) Qt Adaptation To Hr Changesmentioning

confidence: 99%

Techniques for Ventricular Repolarization Instability Assessment From the ECG

2016

View full text Add to dashboard Cite

Abstract-Instabilities in ventricular repolarization have been documented to be tightly linked to arrhythmia vulnerability. Translation of the information contained in the repolarization phase of the ECG into valuable clinical decision-making tools remains challenging. This work aims at providing an overview of the last advances in the proposal and quantification of ECG-derived indices that describe repolarization properties and whose alterations are related with threatening arrhythmogenic conditions. A review of the state-of-the-art is provided, spanning from the electrophysiological basis of ventricular repolarization to its characterization on the surface ECG through a set of temporal and spatial risk markers.Index Terms-Electrophysiological basis of the ECG, ECG waves, ECG intervals, repolarization instabilities, spatial and temporal ventricular repolarization dispersion, cardiac arrhythmias, biophysical modeling of the ECG, ECG signal processing, repolarization risk markers, T wave alternans, QT variability.

show abstract

Effects of stochastic channel gating and distribution on the cardiac action potential

Cited by 41 publications

References 46 publications

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Techniques for Ventricular Repolarization Instability Assessment From the ECG

Contact Info

Product

Resources

About