Abstract
The goal of this paper is two fold. First, we attempt to review the reports available on the role of IKs in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that IKs blockade will lengthen the action potential. However, results obtained with IKs blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongation of action potentials were equally obtained. Although these contradictory results were explained by interspecies or regional differences, the role of IKs in repolarization is a matter of growing dispute. In the second part of this study, we simulated the performance of IKs during cardiac action potentials. We compared the profile of the predicted current in three mathematical models in order to determine the relative role of the current in repolarization. We studied the effect of the cycle length, action potential duration and height of the plateau on the profile of IKs in epicardiac, endocardiac and midmyocardiac ventricular action potentials. The results indicate that the height of the plateau is the most important parameter to control activation of IKs in cardiac tissues, and accordingly, the interspecies and regional differences observed in the efficacy of IKs blockers are likely due to the known differences in action potential morphology. We conclude also that IKs blockade may have unpredictable effects on the length of the action potential in a diseased heart, questioning the possible therapeutic value of drugs blocking IKs.
Keywords: cardiac repolarization, antiarrhythmic drugs, potassium currents, action potentials, computer simulation, reverse use-dependency, iks blockers
Current Medicinal Chemistry
Title: Profile of IKs During the Action Potential Questions the Therapeutic Value of IKs Blockade
Volume: 11 Issue: 1
Author(s): Tamas Banyasz, Roland Koncz, Laszlo Fulop, Norbert Szentandrassy, Janos Magyar and Peter P. Nanasi
Affiliation:
Keywords: cardiac repolarization, antiarrhythmic drugs, potassium currents, action potentials, computer simulation, reverse use-dependency, iks blockers
Abstract: The goal of this paper is two fold. First, we attempt to review the reports available on the role of IKs in myocardial repolarization. Based on theoretical considerations and experimental results, it seems reasonable to assume that IKs blockade will lengthen the action potential. However, results obtained with IKs blockers, like chromanol 293B or L-735,821, are conflicting, since from slight lengthening to marked prolongation of action potentials were equally obtained. Although these contradictory results were explained by interspecies or regional differences, the role of IKs in repolarization is a matter of growing dispute. In the second part of this study, we simulated the performance of IKs during cardiac action potentials. We compared the profile of the predicted current in three mathematical models in order to determine the relative role of the current in repolarization. We studied the effect of the cycle length, action potential duration and height of the plateau on the profile of IKs in epicardiac, endocardiac and midmyocardiac ventricular action potentials. The results indicate that the height of the plateau is the most important parameter to control activation of IKs in cardiac tissues, and accordingly, the interspecies and regional differences observed in the efficacy of IKs blockers are likely due to the known differences in action potential morphology. We conclude also that IKs blockade may have unpredictable effects on the length of the action potential in a diseased heart, questioning the possible therapeutic value of drugs blocking IKs.
Export Options
About this article
Cite this article as:
Banyasz Tamas, Koncz Roland, Fulop Laszlo, Szentandrassy Norbert, Magyar Janos and Nanasi P. Peter, Profile of IKs During the Action Potential Questions the Therapeutic Value of IKs Blockade, Current Medicinal Chemistry 2004; 11 (1) . https://dx.doi.org/10.2174/0929867043456304
DOI https://dx.doi.org/10.2174/0929867043456304 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Novel Nano Drug Systems for Cardiovascular Applications
Recent Patents on Biomedical Engineering (Discontinued) Prediction of Tetralogy of Fallot using Fuzzy Clustering
Recent Advances in Computer Science and Communications Benefits of Olive Oil Phenolic Compounds in Disease Prevention
Endocrine, Metabolic & Immune Disorders - Drug Targets Editorial [Hot Topic Intracellular Calcium Signaling: Holding the Balance between Health and Disease Guest Editor: Luca Munaron]
Current Medicinal Chemistry Recent Advances in Endocrine Metabolic Immune Disorders Drug Targeting: An Editorial Overview
Endocrine, Metabolic & Immune Disorders - Drug Targets A New Practice: Study on the Molecular Mechanism of Traditional Chinese Medicine by Computational Pharmacology Methods: Part 1: Pharmacokinetic Modeling and Chemical Space Distribution
Letters in Drug Design & Discovery Patent Selections
Recent Patents on Biotechnology Cancer Stem Cells: A Novel Paradigm for Cancer Prevention and Treatment
Mini-Reviews in Medicinal Chemistry Curcumin as an Anti-Cancer Agent: Review of the Gap Between Basic and Clinical Applications
Current Medicinal Chemistry Fenofibrate: Metabolic and Pleiotropic Effects
Current Vascular Pharmacology Implications of Pharmacogenetics for Oral Anticoagulants Metabolism
Current Drug Metabolism Triggering Receptor Expressed on Myeloid Cells (TREM) Family and the Application of Its Antagonists
Recent Patents on Anti-Infective Drug Discovery Development and Characterization of Spray Dried Microparticles for Pulmonary Delivery of Antifungal Drug
Current Drug Delivery Molecular Signals Elicited by GPCR Agonists in Hypertension, Cardiovascular Remodeling: Are MMPs and ADAMs Elusive Therapeutic Targets?
Current Hypertension Reviews Editorial (Thematic Issue: Biomarkers of Impaired Innate and Adaptive Immunity in Health and Disease)
Current Immunology Reviews (Discontinued) Pediatric Immune Dysfunction and Health Risks Following Early-Life Immune Insult
Current Pediatric Reviews Dietary Interventions for Atopic Disorders
Current Pharmaceutical Design HIV: A Raft-Targeting Approach for Prevention and Therapy Using Plant-Derived Compounds (Review)
Current Drug Targets Diabetes in Racial and Ethnic Minorities in the United States: Individualizing Approaches to Diagnosis and Management
Current Diabetes Reviews Prognostic Significance of Asymptomatic Myocardial Ischemia in Women vs. Men
Current Pharmaceutical Design