The cardiac transient outward potassium current (referred to as I_to1 or I_to ) is one of the

ion current Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...

s across the cell membrane of

heart muscle cells 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 ...

. It is the main contributing current during the repolarizing phase 1 of the cardiac action potential. It is a result of the movement of positively charged

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

(K⁺) ions from the

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

to the

extracellular space Extracellular space refers to the part of a multicellular organism outside the cells, usually taken to be outside the plasma membranes, and occupied by fluid. This is distinguished from intracellular space, which is inside the cells. The compositi ...

. I_to1 is complemented with I_to2 resulting from Cl⁻ ions to form the transient outward current I_to.

Mechanism

I_to1 is rapidly activated and deactivated. It is activated after the fast increase of the membrane potential following the phase 0 of the cardiac action potential. Once activated, (K⁺) ions from inside the cells flow to the extracellular space. This outward flow of positively charged ions constitutes the I_to1 and causes the

transmembrane voltage Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...

to decrease. This decrease of the transmembrane potential is known as

repolarization In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarizat ...

. I_to1 is then quickly deactivated, stopping the repolarization and ending the phase 1 of the action potential. I_to1 is Ca²⁺-independent and has been clearly demonstrated in myocytes from different cardiac regions and species. There are two kinetic variants of cardiac I_to1: fast I_to1, called I_to1,f, and slow Ito, called I_to1,s. The channel responsible for I_to1,f is formed by assembly of

Kv4.2 Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the ''KCND2'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase ...

(KCND2) subunits,

Kv4.3 Potassium voltage-gated channel subfamily D member 3 also known as Kv4.3 is a protein that in humans is encoded by the ''KCND3'' gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the r ...

(KCND3) subunits or a combination of the two, while the channel responsible for I_to1,s is composed of Kv1.4 (KCNA4) subunits. In addition, several regulatory subunits and pathways modulating the level and biophysical properties of cardiac I_to have been identified. I_to1 affects the opening of Ca²⁺ channels during Phase 2 of the Action Potential. As a result, changes in I_to1 modulate changes in the action potential duration.

Role in disease

*Reduction in I_to1 density is associated with prolonged action potentials and is a common finding in

cardiac disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...

. :*I_to1 density is significantly lower in the cells of a failing heart in comparison to the cells of a healthy heart. :*There is correlation between decreased I_to1 density and atrial fibrillation. :*I_to activation is inhibited by

thyrotropin Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of ...

(TSH). This mechanisms may be one of the reasons for the observation that both bradycardia and atrial fibrillation are common in hypothyroidism. *An increase in the I_to1 density caused by a mutation in Kv4.3 can be a cause of

Brugada Syndrome Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. Those affected may have episodes of syncope ...

References

{{reflist Electrophysiology Cardiac electrophysiology