High intracellular Na<sup>+</sup> preserves myocardial function at low heart rates in isolated myocardium from failing hearts

Schillinger, Wolfgang; Teucher, Nils; Christians, Claus; Kohlhaas, M; Sossalla, Samuel; Nguyen, Phuc Van; Schmidt, Albrecht; Schunck, O.; Nebendahl, Klaus; Maier, Lars S.; Zeitz, Oliver; Hasenfuß, Gerd

doi:10.1016/j.ejheart.2006.01.013

Cited by 22 publications

(21 citation statements)

References 18 publications

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“…At slow pacing rates, the reverse mode of NCX current may promote Ca i transport and SR Ca loading with enhanced SR Ca release. 23, 24 The increased Ca i results in more I KAS activation. Apamin therefore has greater effects at very long PCL than at the intermediate PCL.…”

Section: Discussionmentioning

confidence: 99%

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Hsieh

Chang

Hsueh

et al. 2013

Circ: Arrhythmia and Electrophysiology

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Background Apamin-sensitive K currents (IKAS) are upregulated in heart failure (HF). We hypothesize that apamin can flatten action potential duration restitution (APDR) curve and reduce ventricular fibrillation (VF) duration in failing ventricles. Methods and Results We simultaneously mapped membrane potential and intracellular Ca (Cai) in 7 rabbits hearts with pacing-induced HF and in 7 normal hearts. A dynamic pacing protocol was used to determine APDR at baseline and after apamin (100 nM) infusion. Apamin did not change APD80 in normal ventricles, but prolonged APD80 in failing ventricles at either long (≥300 ms) or short (≤170 ms) pacing cycle length (PCL), but not at intermediate PCL. The maximal slope of APDR curve was 2.03 [95% CI, 1.73 to 2.32] in failing ventricles and 1.26 [95% CI, 1.13 to 1.40] in normal ventricles at baseline (p=0.002). After apamin administration, the maximal slope of APDR in failing ventricles decreased to 1.43 [95% CI, 1.01 to 1.84] (p=0.018) whereas no significant changes were observed in normal ventricles. During VF in failing ventricles, the number of phase singularities (baseline vs apamin, 4.0 vs 2.5), dominant frequency (13.0 Hz vs 10.0 Hz), and VF duration (160 s vs 80 s) were all significantly (p<0.05) decreased by apamin. Conclusions Apamin prolongs APD at long and short, but not at intermediate PCL in failing ventricles. IKAS upregulation may be antiarrhythmic by preserving the repolarization reserve at slow heart rate, but is proarrhythmic by steepening the slope of APDR curve which promotes the generation and maintenance of VF.

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Section: Discussionmentioning

confidence: 99%

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Hsieh

Chang

Hsueh

et al. 2013

Circ: Arrhythmia and Electrophysiology

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“…[Na + ] i is elevated in heart failure (HF), both in humans and in animal models [137,139–142]. By favoring more Ca 2+ influx via NCX, elevated [Na + ] i may limit the contractile dysfunction in HF.…”

Section: [Na+]i Balance In the Failing Heartmentioning

confidence: 99%

Na+ transport in the normal and failing heart — Remember the balance

Despa

Bers

2013

Journal of Molecular and Cellular Cardiology

125

145

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In the heart, intracellular Na+ concentration ([Na+]i) is a key modulator of Ca2+ cycling, contractility and cardiac myocyte metabolism. Several Na+ transporters are electrogenic, thus they both contribute to shaping the cardiac action potential and at the same time are affected by it. [Na+]i is controlled by the balance between Na+ influx through various pathways, including the Na+/Ca2+ exchanger and Na+ channels, and Na+ extrusion via the Na+/K+-ATPase. [Na+]i is elevated in HF due to a combination of increased entry through Na+ channels and/or Na+/H+ exchanger and reduced activity of the Na+/K+-ATPase. Here we review the major Na+ transport pathways in cardiac myocytes and how they participate in regulating [Na+]i in normal and failing hearts.

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“…In myocytes from failing hearts, [Na + ] i is increased by 2–6 mM compared with non‐failing myocytes . In a rabbit HF model, induced by pressure‐overload and volume‐overload, an increased TTX‐sensitive Na + influx has been shown .…”

Section: Sodium Homeostasis and The Plateau Sodium Current In Heart Fmentioning

confidence: 99%

The late sodium current in heart failure: pathophysiology and clinical relevance

Horváth

Bers

2014

ESC Heart Failure

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Large and growing body of data suggest that an increased late sodium current (I Na,late) can have a significant pathophysiological role in heart failure and other heart diseases. The first goal of this article is to describe how I Na,late functions under physiological circumstances. The second goal is to show the wide range of cellular mechanisms that can increase I Na,late in cardiac disease, and also to describe how the up-regulated I Na,late contributes to the pathophys-iology of heart failure. The final section of the article discusses the possible use of I Na,late-modifying drugs in heart failure, on the basis of experimental and preclinical data.

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High intracellular Na⁺ preserves myocardial function at low heart rates in isolated myocardium from failing hearts

Cited by 22 publications

References 18 publications

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Na+ transport in the normal and failing heart — Remember the balance

The late sodium current in heart failure: pathophysiology and clinical relevance

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High intracellular Na+ preserves myocardial function at low heart rates in isolated myocardium from failing hearts

Cited by 22 publications

References 18 publications

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Apamin-Sensitive Potassium Current Modulates Action Potential Duration Restitution and Arrhythmogenesis of Failing Rabbit Ventricles

Na+ transport in the normal and failing heart — Remember the balance

The late sodium current in heart failure: pathophysiology and clinical relevance

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Product

Resources

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High intracellular Na⁺ preserves myocardial function at low heart rates in isolated myocardium from failing hearts