Afterdepolarizations are abnormal

depolarization In biology, depolarization or hypopolarization is a change within a cell (biology), cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolar ...

s of cardiac myocytes that interrupt phase 2, phase 3, or phase 4 of the

cardiac action potential Unlike the action potential in skeletal muscle cells, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as pacemaker cells, that have automatic action potential generati ...

in the

electrical conduction system of the heart The cardiac conduction system (CCS, also called the electrical conduction system of the heart) transmits the Cardiac action potential, signals generated by the sinoatrial node – the heart's Cardiac pacemaker, pacemaker, to cause the heart musc ...

. Afterdepolarizations may lead to

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – above 100 beat ...

s. Afterdepolarization is commonly a consequence of

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

cardiac hypertrophy Ventricular hypertrophy (VH) is thickening of the walls of a ventricle (lower chamber) of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventr ...

, or

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

. It may also result from congenital mutations associated with

calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...

and sequestration. __TOC__

Early afterdepolarizations

Early afterdepolarizations (EADs) occur with abnormal depolarization during phase 2 or phase 3, and are caused by an increase in the frequency of abortive

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

s before normal repolarization is completed. EADs most commonly originate in mid-

myocardial Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

cells and

Purkinje fibers The Purkinje fibers, named for Jan Evangelista Purkyně, ( ; ; Purkinje tissue or subendocardial branches) are located in the inner ventricular walls of the heart, just beneath the endocardium in a space called the subendocardium. The Purki ...

, but can develop in other cardiac cells that carry an action potential. Phase 2 may be interrupted due to augmented opening of calcium channels, while phase 3 interruptions are due to the opening of

sodium channel Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell (biology), cell's cell membrane, membrane. They belong to the Cation channel superfamily, superfamily of cation channels. Classific ...

s. Early afterdepolarizations can result in

torsades de pointes ''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP; also called ''torsades'') (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorph ...

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

, and other

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

s. EADs can be triggered by

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an a ...

and drugs that prolong the

QT interval The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...

, including class Ia and III

antiarrhythmic agents Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a class of drugs that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. ...

, as well as

catecholamines A catecholamine (; abbreviated CA), most typically a 3,4-dihydroxyphenethylamine, is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine. ...

. Afterhyperpolarizations can also occur in cortical pyramidal neurons. There, they typically follow an action potential and are mediated by voltage gated sodium or chloride channels. This phenomenon requires potassium channels to close quickly to limit repolarization. It is responsible for the difference between regular spiking and intrinsically bursting pyramidal neurons.

Delayed afterdepolarizations

Delayed afterdepolarizations (DADs) begin during phase 4, after repolarization is completed but before another action potential would normally occur via the normal conduction systems of the heart. They are due to elevated cytosolic

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

concentrations, classically seen with

digoxin Digoxin (better known as digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart disease, heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ...

toxicity.Katzung, B: ''Basic and Clinical Pharmacology'' (10th ed.), chapter 14: "Agents Used in Cardiac Arrhythmias", The McGraw-Hill Companies, 2007, Lilly, L: "Pathophysiology of Heart Disease", chapter 11: "Mechanisms of Cardiac Arrhthmias", Lippencott, Williams and Wilkens, 2007 The overload of the sarcoplasmic reticulum may cause spontaneous Ca²⁺ release after repolarization, causing the released Ca²⁺ to exit the cell through the 3Na⁺/Ca²⁺-exchanger. This results in a net depolarizing current. The classical feature is Bidirectional

ventricular tachycardia Ventricular tachycardia (V-tach or VT) is a cardiovascular disorder in which fast heart rate occurs in the ventricles of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple ...

. Also seen in

catecholaminergic polymorphic ventricular tachycardia Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur du ...

(CPVT). Delayed afterdepolarization is also seen in myocardial infarction. Purkinje fibers which survive myocardial infarction remain partially depolarized due to its high concentration of cations. Partially depolarized tissue fires rapidly resulting in delayed after depolarization.

References

{{reflist Membrane biology Cardiac electrophysiology