Abstract
Normal heart function and repolarization of the cardiac action potential (AP) is to a high extent subjective to synchronized activity of sarcolemmal K+ channels, expressed in both ventricular and atrial myocardium, largely contributing to regulation of the resting potential, the pacemaker activity, and the shape and duration of the AP. Clinical observations and experimental studies in cardiomyocytes and multicellular preparations provided firm evidence for the sensitivity of some major outward K+ currents and the corresponding ion channels to shifts in intracellular Ca2+ concentration ([Ca2+]i). Direct regulation via interaction between [Ca2+]i and the channel protein or indirect modulation via Ca2+ signaling pathways of these currents have strong implications to mechanical and electrical performance of the heart, and its physiological adaptation to altered load. It may also lead to severe cardiac dysfunction, if [Ca2+]i handling is disturbed in a variety of pathological conditions. In this review we attempt to summarize the present state of the topic on two ubiquitous repolarizing K+ currents (Ito1 and IK1) with documented Ca2+-sensitivity and critical significance in cellular antiarrhythmic defense, to highlight fields where clue data are missing, and discuss the apparently unsolved “mystery” of the cardiac small conductance Ca2+-activated K+ (SK) channels. We have collected the available information on the known novel, although usually still not enough selective inhibitors and activators of these currents justifying the need for more selective ones. Finally, we emphasize a few related therapeutical perspectives to be considered for future experimental research and particularly in pharmaceutical development.
Keywords: Action potential, repolarization, APD, plateau, K+ channel, Ca2+-sensitive, calmodulin, CaMKII, arrhythmia, atrial fibrillation, antiarrhythmic therapy, Ito, IK1, IKca
Current Medicinal Chemistry
Title: Role of Ca2+-Sensitive K+ Currents in Controlling Ventricular Repolarization: Possible Implications for Future Antiarrhytmic Drug Therapy
Volume: 18 Issue: 24
Author(s): N. Nagy, Z. Marton, L. Kiss, A. Varro, P. P. Nanasi and A. Toth
Affiliation:
Keywords: Action potential, repolarization, APD, plateau, K+ channel, Ca2+-sensitive, calmodulin, CaMKII, arrhythmia, atrial fibrillation, antiarrhythmic therapy, Ito, IK1, IKca
Abstract: Normal heart function and repolarization of the cardiac action potential (AP) is to a high extent subjective to synchronized activity of sarcolemmal K+ channels, expressed in both ventricular and atrial myocardium, largely contributing to regulation of the resting potential, the pacemaker activity, and the shape and duration of the AP. Clinical observations and experimental studies in cardiomyocytes and multicellular preparations provided firm evidence for the sensitivity of some major outward K+ currents and the corresponding ion channels to shifts in intracellular Ca2+ concentration ([Ca2+]i). Direct regulation via interaction between [Ca2+]i and the channel protein or indirect modulation via Ca2+ signaling pathways of these currents have strong implications to mechanical and electrical performance of the heart, and its physiological adaptation to altered load. It may also lead to severe cardiac dysfunction, if [Ca2+]i handling is disturbed in a variety of pathological conditions. In this review we attempt to summarize the present state of the topic on two ubiquitous repolarizing K+ currents (Ito1 and IK1) with documented Ca2+-sensitivity and critical significance in cellular antiarrhythmic defense, to highlight fields where clue data are missing, and discuss the apparently unsolved “mystery” of the cardiac small conductance Ca2+-activated K+ (SK) channels. We have collected the available information on the known novel, although usually still not enough selective inhibitors and activators of these currents justifying the need for more selective ones. Finally, we emphasize a few related therapeutical perspectives to be considered for future experimental research and particularly in pharmaceutical development.
Export Options
About this article
Cite this article as:
Nagy N., Marton Z., Kiss L., Varro A., P. Nanasi P. and Toth A., Role of Ca2+-Sensitive K+ Currents in Controlling Ventricular Repolarization: Possible Implications for Future Antiarrhytmic Drug Therapy, Current Medicinal Chemistry 2011; 18 (24) . https://dx.doi.org/10.2174/092986711796642463
DOI https://dx.doi.org/10.2174/092986711796642463 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Update on the Pharmacological Treatment of Alzheimers Disease
Current Neuropharmacology Cardioprotection Acquired Through Exercise: The Role of Ischemic Preconditioning
Current Cardiology Reviews Mobile Phone Based Biomedical Imaging Technology: A Newly Emerging Area
Recent Patents on Biomedical Engineering (Discontinued) Effects of Obesity on Vascular Potassium Channels
Current Vascular Pharmacology Glucagon-Like Peptide-1 as a Key Regulator of Lipid and Lipoprotein Metabolism in Fasting and Postprandial States
Cardiovascular & Hematological Disorders-Drug Targets An Augmented Passive Immune Therapy to Treat Fulminant Bacterial Infections
Recent Patents on Anti-Infective Drug Discovery Food and Food Supplements with Hypocholesterolemic Effects
Recent Patents on Food, Nutrition & Agriculture Current Paradigms in COVID-19 Research: Proposed Treatment Strategies, Recent Trends and Future Directions
Current Medicinal Chemistry Advent and Maturation of Regenerative Medicine
Current Stem Cell Research & Therapy The Long Pentraxin PTX3, a Soluble Pattern Recognition Receptor Involved in Innate Immunity,Inflammation and Female Fertility
Current Immunology Reviews (Discontinued) Antiplatelet Therapy in TAVI: Current Clinical Practice and Recommendations
Current Pharmaceutical Design 1,8-Naphthyridine Derivatives: A Privileged Scaffold for Versatile Biological Activities
Mini-Reviews in Medicinal Chemistry Role of Galectins in Allergic Disorders
Recent Patents on Inflammation & Allergy Drug Discovery Stem Cell Therapy in Chronic Ischemic Heart Dysfunction with and Without Viability
Cardiovascular & Hematological Disorders-Drug Targets Medicinal Plants for the Prevention and Treatment of Bacterial Infections
Current Pharmaceutical Design The “Aged Garlic Extract” (AGE) and One of its Active Ingredients S-Allyl-LCysteine (SAC) as Potential Preventive and Therapeutic Agents for Alzheimer's Disease (AD)
Current Medicinal Chemistry Oxidative Stress Modulation Through Habitual Physical Activity
Current Pharmaceutical Design Folate and Homocysteine Metabolism: Therapeutic Targets in Cardiovascular and Neurodegenerative Disorders
Current Medicinal Chemistry Medical Devices for Telemedicine and Home Care Applications
Recent Patents on Biomedical Engineering (Discontinued) Regulation of Stem Cell-Based Research in India in Comparison with the US, EU and other Asian Countries: Current Issues and Future Perspectives
Current Stem Cell Research & Therapy