Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models
Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to con...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.620539/full |
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| author | Gary Tse Gary Tse Ka Hou Christien Li Chloe Kwong Yee Cheung Konstantinos P. Letsas Aishwarya Bhardwaj Abhishek C. Sawant Tong Liu Gan-Xin Yan Henggui Zhang Kamalan Jeevaratnam Nazish Sayed Nazish Sayed Nazish Sayed Shuk Han Cheng Shuk Han Cheng Shuk Han Cheng Wing Tak Wong |
| author_facet | Gary Tse Gary Tse Ka Hou Christien Li Chloe Kwong Yee Cheung Konstantinos P. Letsas Aishwarya Bhardwaj Abhishek C. Sawant Tong Liu Gan-Xin Yan Henggui Zhang Kamalan Jeevaratnam Nazish Sayed Nazish Sayed Nazish Sayed Shuk Han Cheng Shuk Han Cheng Shuk Han Cheng Wing Tak Wong |
| author_sort | Gary Tse |
| collection | DOAJ |
| description | Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD–ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis. |
| first_indexed | 2024-12-14T03:15:04Z |
| format | Article |
| id | doaj.art-498fcb99673743cf8e52f6399c964b62 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-14T03:15:04Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-498fcb99673743cf8e52f6399c964b622022-12-21T23:19:10ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-02-01810.3389/fcvm.2021.620539620539Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical ModelsGary Tse0Gary Tse1Ka Hou Christien Li2Chloe Kwong Yee Cheung3Konstantinos P. Letsas4Aishwarya Bhardwaj5Abhishek C. Sawant6Tong Liu7Gan-Xin Yan8Henggui Zhang9Kamalan Jeevaratnam10Nazish Sayed11Nazish Sayed12Nazish Sayed13Shuk Han Cheng14Shuk Han Cheng15Shuk Han Cheng16Wing Tak Wong17Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, ChinaFaculty of Health and Medical Sciences, University of Surrey, Guildford, United KingdomFaculty of Medicine, Newcastle University, Newcastle upon Tyne, United KingdomLi Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, ChinaSecond Department of Cardiology, Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Athens, GreeceDivision of Cardiology, Department of Internal Medicine, State University of New York at Buffalo, Buffalo, NY, United StatesDivision of Cardiology, Department of Internal Medicine, State University of New York at Buffalo, Buffalo, NY, United StatesTianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, ChinaLankenau Institute for Medical Research and Lankenau Medical Center, Wynnewood, PA, United StatesSchool of Physics and Astronomy, The University of Manchester, Manchester, United KingdomFaculty of Health and Medical Sciences, University of Surrey, Guildford, United KingdomStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, United States0Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, United States1Department of Medicine, Division of Cardiology, Stanford University School of Medicine, Stanford, CA, United States2Department of Biomedical Sciences, College of Veterinary Medicine and Life Science, City University of Hong Kong, Hong Kong, China3State Key Laboratory of Marine Pollution (SKLMP), City University of Hong Kong, Hong Kong, China4Department of Materials Science and Engineering, College of Science and Engineering, City University of Hong Kong, Hong Kong, China5School of Life Sciences, Chinese University of Hong Kong, Hong Kong, ChinaPotassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD–ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.https://www.frontiersin.org/articles/10.3389/fcvm.2021.620539/fullhypokalaemiapotassiumcardiac arrhythmiaconductionrepolarization |
| spellingShingle | Gary Tse Gary Tse Ka Hou Christien Li Chloe Kwong Yee Cheung Konstantinos P. Letsas Aishwarya Bhardwaj Abhishek C. Sawant Tong Liu Gan-Xin Yan Henggui Zhang Kamalan Jeevaratnam Nazish Sayed Nazish Sayed Nazish Sayed Shuk Han Cheng Shuk Han Cheng Shuk Han Cheng Wing Tak Wong Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models Frontiers in Cardiovascular Medicine hypokalaemia potassium cardiac arrhythmia conduction repolarization |
| title | Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models |
| title_full | Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models |
| title_fullStr | Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models |
| title_full_unstemmed | Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models |
| title_short | Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models |
| title_sort | arrhythmogenic mechanisms in hypokalaemia insights from pre clinical models |
| topic | hypokalaemia potassium cardiac arrhythmia conduction repolarization |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.620539/full |
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