Afterdepolarizations are abnormal

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

s of

cardiac myocyte Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

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

cardiac action potential The cardiac action potential is a brief change in voltage ( membrane potential) across the cell membrane of heart cells. This is caused by the movement of charged atoms (called ions) between the inside and outside of the cell, through proteins c ...

in the

electrical conduction system of the heart The cardiac conduction system (CCS) (also called the electrical conduction system of the heart) transmits the signals generated by the sinoatrial node – the heart's pacemaker, to cause the heart muscle to contract, and pump blood through the ...

. Afterdepolarizations may lead to

cardiac arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

s. Afterdepolarization is commonly a consequence of

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, cardiac hypertrophy, or

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

. 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, although there are also ligand-gated calcium channels. Comparison tables The following tables ex ...

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 occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells, ...

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

myocardial Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

cells and

Purkinje fibers The Purkinje fibers (; often incorrectly ; 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 Purkinje fibers are specia ...

, 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's membrane. They belong to the superfamily of cation channels and can be classified according to the trigger that opens the channel ...

s. Early afterdepolarizations can result in

torsades de pointes ''Torsades de pointes, torsade de pointes'' or ''torsades des pointes'' (TdP) (, , translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia t ...

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 (su ...

, and other

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

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 abno ...

and drugs that prolong the

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

, including class Ia and III

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

, as well as

catecholamines A catecholamine (; abbreviated CA) 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. Catechol can be either a free molecule or a substi ...

. 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 with the 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 ...

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 conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...

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 fast heart rate arising from the lower chambers of the heart. Although a few seconds of VT may not result in permanent problems, longer periods are dangerous; and multiple episodes over a short period ...

. 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

Membrane biology Cardiac electrophysiology {{circulatory-disease-stub