Related Experiment Video

Updated: May 5, 2026

Programmed Electrical Stimulation in Mice
07:29

Programmed Electrical Stimulation in Mice

Published on: May 27, 2010

20.3K

Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial fibrillation

Anil Purohit1, Adam G Rokita, Xiaoqun Guan

  • 1Department of Internal Medicine, Division of Cardiovascular Medicine and Cardiovascular Research Center, Carver College of Medicine (A.P., A.G.R., X.G., B.C., O.M.K., Z.G., E.D.L., H.S., A.C.B., R.N.E.-A., P.D.S., R.M.W., L.-S.S., M.E.A.), Department of Obstetrics and Gynecology (B.Y.), and Department of Molecular Physiology and Biophysics (M.E.A.), University of Iowa, Iowa City; Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany, and Division of Experimental Cardiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany (N.V., D.D.); Cardiology and Pneumology, German Heart Center, University Hospital Goettingen, Goettingen, Germany (S.N., T.S., L.S.M.); and Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX (N.L., X.H.T.W.).

Circulation
|September 14, 2013
PubMed
Abstract

Insights

Oxidized Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is linked to atrial fibrillation (AF). Reducing oxidized CaMKII may offer new therapies for AF patients.

Area of Science:

  • Cardiovascular Research
  • Molecular Cardiology
  • Biochemistry

Background:

  • Atrial fibrillation (AF) is a significant public health concern with limited therapeutic options.
  • Angiotensin II and reactive oxygen species (ROS) are known risk factors for AF, but the underlying molecular mechanisms remain unclear.
  • Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a newly identified ROS-activated proarrhythmic signal.

Purpose of the Study:

  • To investigate the role of oxidized CaMKIIδ in the development of AF.
  • To determine if CaMKII acts as a molecular link between ROS and AF.
  • To explore potential therapeutic strategies targeting oxidized CaMKII for AF prevention.

Main Methods:

  • Comparison of oxidized CaMKII levels in atrial tissue from AF patients versus sinus rhythm patients.
  • Assessment of AF susceptibility in mice infused with angiotensin II.
  • Utilizing knock-in mice with modified CaMKIIδ oxidation sites (MM-VV) and transgenic mice overexpressing methionine sulfoxide reductase A.

Main Results:

  • Oxidized CaMKII was elevated in atria of AF patients and angiotensin II-treated mice.
  • Angiotensin II infusion increased AF susceptibility in wild-type mice.
  • MM-VV CaMKIIδ knock-in mice and methionine sulfoxide reductase A-overexpressing mice showed resistance to AF induction.

Conclusions:

  • CaMKII serves as a molecular mediator connecting increased ROS to AF.
  • Therapeutic interventions aimed at reducing oxidized CaMKII may hold promise for preventing or mitigating AF.
Keywords:
angiotensin IIarrhythmias, cardiacatrial fibrillationcalcium-calmodulin-dependent protein kinase type IIreactive oxygen species

More Related Videos

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents10:53

Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents

Published on: July 3, 2013

22.2K
Optimization of Transesophageal Atrial Pacing to Assess Atrial Fibrillation Susceptibility in Mice08:05

Optimization of Transesophageal Atrial Pacing to Assess Atrial Fibrillation Susceptibility in Mice

Published on: June 29, 2022

2.9K

Related Concept Videos

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
5.5K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.0K
Mechanism of Cardiac Arrhythmias01:28

Mechanism of Cardiac Arrhythmias

Arrhythmias are irregular heart rhythms occurring when the heart's electrical impulses become abnormal. These disturbances can lead to various symptoms, depending on their severity and the underlying cause. Some common factors contributing to arrhythmias include hypoxia, ischemia, electrolyte imbalances, excessive catecholamine exposure, drug toxicity, and muscle overstretching. Arrhythmias can be classified into two main types based on the rate and site of origin of abnormal heart rhythms.
2.7K
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
2.3K
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
2.9K
Disturbances in Heart Rhythm01:29

Disturbances in Heart Rhythm

Arrhythmia or dysrhythmia refers to an abnormal heart rhythm caused by a defect in the heart's conduction system. It can cause the heart to beat irregularly, too quickly, or too slowly, leading to symptoms like chest pain, shortness of breath, and fainting. Factors such as stress, caffeine, alcohol, nicotine, cocaine, certain drugs, congenital defects, diseases, and electrolyte abnormalities can trigger arrhythmias.
Arrhythmias are categorized by their speed, rhythm, and origin. A slow heart...
5.3K