The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Dierk Thomas - One of the best experts on this subject based on the ideXlab platform.
-
The human cardiac K_2P3.1 (TASK-1) potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-Schmiedeberg's Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Eberhard Scholz, Christoph Karle, Hugo A. Katus, Dierk ThomasAbstract:Two-pore-domain (K_2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K_2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I _ KP . Class III antiarrhythmic Drugs target cardiac K^+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K_2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK_2P3.1 currents (IC_50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK_2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK_2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK_2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK_2P3.1 background channels. Amiodarone blockade of hK_2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.
-
the human cardiac k2p3 1 task 1 potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-schmiedebergs Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Hugo A. Katus, Eberhard P Scholz, Christoph A Karle, Dierk ThomasAbstract:Two-pore-domain (K2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I KP . Class III antiarrhythmic Drugs target cardiac K+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK2P3.1 currents (IC50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK2P3.1 background channels. Amiodarone blockade of hK2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.
Mithilesh K. Das - One of the best experts on this subject based on the ideXlab platform.
-
Delayed and indirect effects of antiarrhythmic Drugs in reducing sudden cardiac death
Future cardiology, 2011Co-Authors: Saurabh Malhotra, Mithilesh K. DasAbstract:In the USA, two-thirds of sudden cardiac deaths (SCDs) are caused by sustained ventricular tachycardia and ventricular fibrillation. Implantable cardioverter defibrillator (ICD) therapy has been demonstrated to decrease mortality caused by these arrhythmias, when used both for primary and secondary prevention. However, ICD use is expensive, has proarrhythmic effects and does not prevent ventricular arrhythmias. Antiarrhythmic Drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and SCD. Most commonly, AADs are often used in patients with an ICD who have recurrent ICD shocks due to ventricular arrhythmias. Class I AADs are used in patients with a structurally normal heart and are contraindicated in patients with structural heart disease. β-blockers have been demonstrated to be beneficial in preventing mortality and malignant tachyarrhythmias in postmyocardial infarction and congestive heart failure patients, and in patients who have an ICD. Amiodarone has a neutral effect on mortality, while other Class III Drugs may increase mortality in certain subgroups of patients. Dronedarone, a new Class III Drug, may reduce mortality, but sufficient data are not available to allow for its use in the prevention of malignant tachyarrhythmias. Few Drugs that are not Classified as AADs can also prevent arrhythmias, via their beneficial effects on cardiovascular remodeling. These non-ADDs have delayed and indirect effects, which are mediated by the renin-angiotensin-aldosterone system and lipid metabolism - n-3 polyunsaturated fatty acids (fish oil), and statins, and can thus can reduce the likelihood of future malignant ventricular arrhythmias in patients with coronary artery disease or congestive heart failure. The role of chronic Drug therapy alone for primary and secondary prevention of SCD is less than desirable because of proarrhythmic and adverse side effects. The non-ADDs are well tolerated and have no proarrhythmic actions, thus their benefit could outweigh risks, although currently there are no concrete data to suggest this.
-
Antiarrhythmic and nonantiarrhythmic Drugs for sudden cardiac death prevention.
Journal of cardiovascular pharmacology, 2010Co-Authors: Mithilesh K. Das, Douglas P. ZipesAbstract:Life-threatening ventricular arrhythmias such as sustained ventricular tachycardia and ventricular fibrillation are responsible for two thirds of sudden cardiac deaths annually in the United States. Implantable cardioverter-defibrillator (ICD) therapy prevents mortality from arrhythmic death but is expensive and has some associated morbidity from proarrhythmia and mechanical malfunction. Furthermore, ICDs treat ventricular arrhythmias but do not prevent them. Antiarrhythmic Drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and sudden cardiac deaths. AADS are often used in patients with an ICD who have recurrent ICD shocks resulting from ventricular arrhythmias. Class I AADs are contraindicated in patients with structural heart disease. Other than amiodarone, all Class III Drugs have either a neutral or deleterious effect on mortality. Dronedarone, a new Class III Drug, may reduce mortality, but more information is needed to be sure. A Class of Drugs that do not qualify as an AAD can modify cardiovascular remodeling processes and have a delayed and indirect antiarrhythmic effect. These so-called "nonantiarrhythmic Drugs" such as Drugs acting on the renin-angiotensin-aldosterone system, fish oil, and statins can reduce the likelihood of future ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease or congestive heart failure. The role of AADs for chronic therapy for primary and secondary prevention of sudden cardiac death is problematic because of proarrhythmia and adverse side effects. Because these nonantiarrhythmic Drugs are well tolerated and have no proarrhythmic actions, their benefits should outweigh risks.
Jakob Gierten - One of the best experts on this subject based on the ideXlab platform.
-
The human cardiac K_2P3.1 (TASK-1) potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-Schmiedeberg's Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Eberhard Scholz, Christoph Karle, Hugo A. Katus, Dierk ThomasAbstract:Two-pore-domain (K_2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K_2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I _ KP . Class III antiarrhythmic Drugs target cardiac K^+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K_2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK_2P3.1 currents (IC_50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK_2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK_2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK_2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK_2P3.1 background channels. Amiodarone blockade of hK_2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.
-
the human cardiac k2p3 1 task 1 potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-schmiedebergs Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Hugo A. Katus, Eberhard P Scholz, Christoph A Karle, Dierk ThomasAbstract:Two-pore-domain (K2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I KP . Class III antiarrhythmic Drugs target cardiac K+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK2P3.1 currents (IC50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK2P3.1 background channels. Amiodarone blockade of hK2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.
Douglas P. Zipes - One of the best experts on this subject based on the ideXlab platform.
-
Antiarrhythmic and nonantiarrhythmic Drugs for sudden cardiac death prevention.
Journal of cardiovascular pharmacology, 2010Co-Authors: Mithilesh K. Das, Douglas P. ZipesAbstract:Life-threatening ventricular arrhythmias such as sustained ventricular tachycardia and ventricular fibrillation are responsible for two thirds of sudden cardiac deaths annually in the United States. Implantable cardioverter-defibrillator (ICD) therapy prevents mortality from arrhythmic death but is expensive and has some associated morbidity from proarrhythmia and mechanical malfunction. Furthermore, ICDs treat ventricular arrhythmias but do not prevent them. Antiarrhythmic Drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and sudden cardiac deaths. AADS are often used in patients with an ICD who have recurrent ICD shocks resulting from ventricular arrhythmias. Class I AADs are contraindicated in patients with structural heart disease. Other than amiodarone, all Class III Drugs have either a neutral or deleterious effect on mortality. Dronedarone, a new Class III Drug, may reduce mortality, but more information is needed to be sure. A Class of Drugs that do not qualify as an AAD can modify cardiovascular remodeling processes and have a delayed and indirect antiarrhythmic effect. These so-called "nonantiarrhythmic Drugs" such as Drugs acting on the renin-angiotensin-aldosterone system, fish oil, and statins can reduce the likelihood of future ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease or congestive heart failure. The role of AADs for chronic therapy for primary and secondary prevention of sudden cardiac death is problematic because of proarrhythmia and adverse side effects. Because these nonantiarrhythmic Drugs are well tolerated and have no proarrhythmic actions, their benefits should outweigh risks.
Patrick A. Schweizer - One of the best experts on this subject based on the ideXlab platform.
-
The human cardiac K_2P3.1 (TASK-1) potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-Schmiedeberg's Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Eberhard Scholz, Christoph Karle, Hugo A. Katus, Dierk ThomasAbstract:Two-pore-domain (K_2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K_2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I _ KP . Class III antiarrhythmic Drugs target cardiac K^+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K_2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK_2P3.1 currents (IC_50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK_2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK_2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK_2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK_2P3.1 background channels. Amiodarone blockade of hK_2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.
-
the human cardiac k2p3 1 task 1 potassium leak channel is a molecular target for the Class III antiarrhythmic Drug amiodarone
Naunyn-schmiedebergs Archives of Pharmacology, 2010Co-Authors: Jakob Gierten, Eckhard Ficker, Ramona Bloehs, Patrick A. Schweizer, Edgar Zitron, Hugo A. Katus, Eberhard P Scholz, Christoph A Karle, Dierk ThomasAbstract:Two-pore-domain (K2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, K2P3.1 (TASK-1) channels are implicated in the cardiac plateau current, I KP . Class III antiarrhythmic Drugs target cardiac K+ currents, resulting in action potential prolongation and suppression of atrial and ventricular arrhythmias. The objective of this study was to investigate acute effects of the Class III antiarrhythmic Drug amiodarone on human K2P3.1 channels. Potassium currents were recorded from Xenopus oocytes using the two-microelectrode voltage clamp technique. Amiodarone produced concentration-dependent inhibition of hK2P3.1 currents (IC50 = 0.40 µM) with maximum current reduction of 58.1%. Open rectification properties that are characteristic to hK2P3.1 currents were not altered by amiodarone. Channels were blocked in open and closed states in reverse frequency-dependent manner. hK2P3.1 channel inhibition was voltage-independent at voltages between −40 and +60 mV. Modulation of protein kinase C activity by amiodarone does not contribute to hK2P3.1 current reduction, as pre-treatment with the protein kinase C inhibitor, staurosporine, did not affect amiodarone block. Amiodarone is an inhibitor of cardiac hK2P3.1 background channels. Amiodarone blockade of hK2P3.1 may cause prolongation of cardiac repolarization and action potential duration in patients with high individual plasma concentrations, possibly contributing to the antiarrhythmic efficacy of the Class III Drug.