Calcium Signaling and Cardiac Arrhythmias

Landstrom, Andrew P.; Dobrev, Dobromir; Wehrens, Xander H.T.

doi:10.1161/circresaha.117.310083

Cited by 413 publications

(366 citation statements)

References 307 publications

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“…Figure 10b. Moreover, as a general remark we want to emphasise that all these approaches can be modified, i.e., we can add weight to the control parameter depending on the system specific properties, as we already did in system (8). In system (8), e.g., we can modifyḠ K andτ x as follows…”

Section: Controlling the Early Afterdepolarisationsmentioning

confidence: 99%

“…The presence of EADs strongly correlates with the onset of dangerous cardiac arrhythmias, including torsades de pointes (TdP), which is a specific type of abnormal heart rhythm that can lead to sudden cardiac death, see [2][3][4]. Please see for more (biological/physiological) details [5][6][7][8][9][10][11]. In this paper, we will use the bifurcation analysis similar to [12][13][14] to study the system introduced in [1].…”

Section: Introductionmentioning

confidence: 99%

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Bifurcation Analysis of a Certain Hodgkin-Huxley Model Depending on Multiple Bifurcation Parameters

Erhardt

2018

Mathematics

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Abstract:In this paper, we study the dynamics of a certain Hodgkin-Huxley model describing the action potential (AP) of a cardiac muscle cell for a better understanding of the occurrence of a special type of cardiac arrhythmia, the so-called early afterdepolarisations (EADs). EADs are pathological voltage oscillations during the repolarisation or plateau phase of cardiac APs. They are considered as potential precursors to cardiac arrhythmia and are often associated with deficiencies in potassium currents or enhancements in the calcium or sodium currents, e.g., induced by ion channel diseases, drugs or stress. Our study is focused on the enhancement in the calcium current to identify regions, where EADs related to enhanced calcium current appear. To this aim, we study the dynamics of the model using bifurcation theory and numerical bifurcation analysis. Furthermore, we investigate the interaction of the potassium and calcium current. It turns out that a suitable increasing of the potassium current adjusted the EADs related to an enhanced calcium current. Thus, one can use our result to balance the EADs in the sense that an enhancement in the potassium currents may compensate the effect of enhanced calcium currents.

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Section: Controlling the Early Afterdepolarisationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bifurcation Analysis of a Certain Hodgkin-Huxley Model Depending on Multiple Bifurcation Parameters

Erhardt

2018

Mathematics

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“…28, 29 By an independent mechanism, activity of CaMKII may be activated due to increased levels of Ca 2+ in the junctional cleft that are associated with decreased NCX activity in AnkB +/− mice. 30 These Ca 2+ sparks can lead to aberrant release of Ca 2+ that compromises the specificity of EC signaling, ultimately increasing the propensity for arrhythmias and electrical dysfunction 31 …”

Section: Role Of Ankyrin-b In Cardiac Excitabilitymentioning

confidence: 99%

The evolving role of ankyrin-B in cardiovascular disease

Koenig

Mohler

2017

Heart Rhythm

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Over the last decade, ankyrin-B has been identified as a prominent player in cardiac physiology. Ankyrin-B has a multitude of functions, with roles in expression, localization, and regulation of proteins critical for cardiac excitability, cytoskeletal integrity, and signaling. Further, human ANK2 variants that result in ankyrin-B loss-of-function are associated with ‘Ankyrin-B syndrome’, a complex cardiac phenotype that may include bradycardia and heart rate variability, conduction block, atrial fibrillation, QT interval prolongation, and potentially fatal catecholaminergic polymorphic ventricular tachycardia. However, our understanding of the molecular mechanisms underlying ankyrin-B function at baseline and in disease is still not fully resolved due to the complexity of ankyrin-B gene regulation, number of ankyrin-B-associated molecules, multiple roles of ankyrin-B in the heart and other organs that modulate cardiac function, and a host of unexpected clinical phenotypes. Here, we summarize known roles of ankyrin-B in the heart and the impact of ankyrin-B dysfunction in animal models and in human disease, as well as highlight important new findings illustrating the complexity of ankyrin-B signaling.

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“…little or no permeability to larger solutes such as propidium cation 10,12,[43][44][45]. Blockers of these currents decreased the amplitude of SSD, thereby increasing the AP threshold.Afterdepolarizations (categorized as early and delayed ones) are important electrophysiological phenomena closely related to myocyte calcium handling and arrhythmogenesis, and usually ascribed to (re)activation of I Ca-L or I NCX , respectively [46][47][48]. I NCX and I Ca-L , though not critical for either SSD development or AP firing, were shown to affect both.…”

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confidence: 99%

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

Azarov

Semenov

Casciola

et al. 2019

Cardiovasc electrophysiol

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Introduction Opening of voltage‐gated sodium channels takes tens to hundreds of microseconds, and mechanisms of their opening by nanosecond pulsed electric field (nsPEF) stimuli remain elusive. This study was aimed at uncovering the mechanisms of how nsPEF elicits action potentials (APs) in cardiomyocytes. Methods and Results Fluorescent imaging of optical APs (FluoVolt) and Ca2+‐transients (Fluo‐4) was performed in enzymatically isolated murine ventricular cardiomyocytes stimulated by 200‐nanosecond trapezoidal pulses. nsPEF stimulation evoked tetrodotoxin‐sensitive APs accompanied or preceded by slow sustained depolarization (SSD) and, in most cells, by transient afterdepolarization waves. SSD threshold was lower than the AP threshold (1.26 ± 0.03 vs 1.34 ± 0.03 kV/cm, respectively, P < 0.001). Inhibition of l‐type calcium and sodium‐calcium exchanger currents reduced the SSD amplitude and increased the AP threshold ( P < 0.05). The threshold for Ca 2+‐transients (1.40 ± 0.04 kV/cm) was not significantly affected by a tetrodotoxin‐verapamil cocktail, suggesting the activation of a Ca 2+ entry pathway independent from the opening of Na + or Ca 2+ voltage‐gated channels. Removal of external Ca 2+ decreased the SSD amplitude ( P = 0.004) and blocked Ca 2+‐transients but not APs. The incidence of transient afterdepolarization waves was decreased by verapamil and by removal of external Ca 2+ ( P = 0.002). Conclusions The study established that nsPEF stimulation caused calcium entry into cardiac myocytes (including routes other than voltage‐gated calcium channels) and SSD. Tetrodotoxin‐sensitive APs were mediated by SSD, whose amplitude depended on the calcium entry. Plasma membrane electroporation was the most likely primary mechanism of SSD with additional contribution from l‐type calcium and sodium‐calcium exchanger currents.

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Calcium Signaling and Cardiac Arrhythmias

Cited by 413 publications

References 307 publications

Bifurcation Analysis of a Certain Hodgkin-Huxley Model Depending on Multiple Bifurcation Parameters

Bifurcation Analysis of a Certain Hodgkin-Huxley Model Depending on Multiple Bifurcation Parameters

The evolving role of ankyrin-B in cardiovascular disease

Excitation of murine cardiac myocytes by nanosecond pulsed electric field

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