Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy

Skogestad, Jonas; Aronsen, Jan Magnus

doi:10.3389/fphys.2018.01500

Cited by 100 publications

(82 citation statements)

References 137 publications

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“…The physiological significance of such pools of Na ϩ is currently unknown, but differential regulation of Na ϩ -dependent processes in distinct compartments allows fine tuning of intracellular processes such as contractility and pH regulation. Several publications have showed that the specific intracellular colocalization of NKA and NCX facilitates tight regulation of cardiac contractility and relaxation (16,21,36) and arrhythmic susceptibility (33). In addition, since the subsarcolemmal space constitutes only a fraction of the total cell volume, less Na ϩ needs to be cycled across the sarcolemma to achieve a large physiological effect, which likely promotes thermodynamic efficiency.…”

Section: Nka-sensed [Na ϩ ] Is High Compared With the Bulk Cytosolmentioning

confidence: 99%

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Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes

Skogestad

Lines

Louch

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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The intracellular Na+ concentration ([Na+]) regulates cardiac contractility. Previous studies have suggested that subsarcolemmal [Na+] is higher than cytosolic [Na+] in cardiac myocytes, but this concept remains controversial. Here, we used electrophysiological experiments and mathematical modeling to test whether there are subsarcolemmal pools with different [Na+] and dynamics compared with the bulk cytosol in rat ventricular myocytes. A Na+ dependency curve for Na+-K+-ATPase (NKA) current was recorded with symmetrical Na+ solutions, i.e., the same [Na+] in the superfusate and internal solution. This curve was used to estimate [Na+] sensed by NKA in other experiments. Three experimental observations suggested that [Na+] is higher near NKA than in the bulk cytosol: 1) when extracellular [Na+] was high, [Na+] sensed by NKA was ~6 mM higher than the internal solution in quiescent cells; 2) long trains of Na+ channel activation almost doubled this gradient; compared with an even intracellular distribution of Na+, the increase of [Na+] sensed by NKA was 10 times higher than expected, suggesting a local Na+ domain; and 3) accumulation of Na+ near NKA after trains of Na+ channel activation dissipated very slowly. Finally, mathematical models assuming heterogeneity of [Na+] between NKA and the Na+ channel better reproduced experimental data than the homogeneous model. In conclusion, our data suggest that NKA-sensed [Na+] is higher than [Na+] in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. NEW & NOTEWORTHY Our data suggest that the Na+-K+-ATPase-sensed Na+ concentration is higher than the Na+ concentration in the bulk cytosol and that there are differential Na+ pools in the subsarcolemmal space, which could be important for cardiac contractility and arrhythmogenesis. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/heterogeneous-sodium-in-ventricular-myocytes/ .

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Section: Nka-sensed [Na ϩ ] Is High Compared With the Bulk Cytosolmentioning

confidence: 99%

“…In contrast, Na ϩ removal by NKA may create local Na ϩ coldspots. Indeed, the ␣ 2 -isoform of NKA regulates [Na ϩ ] sensed by NCX, thereby regulating contractility (1,16,36) and cardiac arrhythmogenesis (33). However, the properties of subsarcolemmal [Na ϩ ] apparently diverge when different Na ϩ transporters are studied.…”

Section: Introductionmentioning

confidence: 99%

Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes

Skogestad

Lines

Louch

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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“…In the general population, plasma potassium levels range from 3.5 to 5.5 mEq/L, and the risk of arrhythmia increases at values below 2.7 mEq/L . In acute experimental models in healthy rat hearts, the potassium level is reduced to 1 mEq/L .…”

Section: Introductionmentioning

confidence: 99%

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

Prado

Beňová

Diez

et al. 2019

Journal of Pineal Research

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Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation.Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent. K E Y W O R D Saction potential, arrhythmias, connexin-43, hypokalemia, melatonin, QRS

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“…During the course of the disease, both the husband and the wife had obvious hypokalemia, and the wife had a brief premature heart beat. Hypokalemia is easy to induce arrhythmia and heart failure [12][13][14][15][16] , even related to some malignant arrhythmias 17 , especially for patients with basic heart disease.…”

Section: Discussionmentioning

confidence: 99%

A Couple with Different Symptoms after Simultaneously 2019-nCoV Infected

Zhang

Tang

et al. 2020

Preprint

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Background 2019-nCoV has posed a significant threat to human health since the epidemic began. So far, there is no definite safe and effective drug treatment. Proper management can help prevent mild patients from becoming severe. We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV and analyze the changes in the diagnosis and treatment process. Case presentation We report a couple with different symptoms after simultaneously infected by the same source of 2019-nCoV in Shandong, China，describe their clinical course，characteristics and detection results in detail, and analyze the changes in the diagnosis and treatment process. The wife was mainly affected by respiratory system and had ever experienced high fever for several days. The husband's condition is lighter than his wife，mainly manifested as digestive tract symptoms，but it took longer than his wife for the nucleic acid of nasopharynx swab for 2019-nCoV to turn negative. Conclusions In the course of the disease both of the couple had hypokalemia which was easy to be corrected. CRP and ESR were consistent with the changes of the disease during the 2019-nCoV infection, which were good indicators to reflect the severity and development of the disease. Two months after discharge, both of them showed negative IgM antibody and positive IgG antibody.

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Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy

Cited by 100 publications

References 137 publications

Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes

Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

A Couple with Different Symptoms after Simultaneously 2019-nCoV Infected

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Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy

Cited by 100 publications

References 137 publications

Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytes

Evidence for heterogeneous subsarcolemmal Na+ levels in rat ventricular myocytes

Melatonin receptor activation protects against low potassium‐induced ventricular fibrillation by preserving action potentials and connexin‐43 topology in isolated rat hearts

A Couple with Different Symptoms after Simultaneously 2019-nCoV Infected

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Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes

Evidence for heterogeneous subsarcolemmal Na⁺ levels in rat ventricular myocytes