cardiac transient outward potassium current

I_to1 is rapidly activated and deactivated.{{cite journal | vauthors = Wettwer E, Amos G, Gath J, Zerkowski HR, Reidemeister JC, Ravens U | title = Transient outward current in human and rat ventricular myocytes | journal = Cardiovascular Research | volume = 27 | issue = 9 | pages = 1662–1669 | date = September 1993 | pmid = 8287446 | doi = 10.1093/cvr/27.9.1662 }} 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 to decrease. This decrease of the transmembrane potential is known as repolarization. I_to1 is then quickly deactivated, stopping the repolarization and ending the phase 1 of the action potential.

I_to1 is Ca²⁺-independent{{cite journal | vauthors = Oudit GY, Kassiri Z, Sah R, Ramirez RJ, Zobel C, Backx PH | title = The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium | journal = Journal of Molecular and Cellular Cardiology | volume = 33 | issue = 5 | pages = 851–872 | date = May 2001 | pmid = 11343410 | doi = 10.1006/jmcc.2001.1376 | s2cid = 829154 }} 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 (KCND2) subunits, Kv4.3 (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.

• Reduction in I_to1 density is associated with prolonged action potentials and is a common finding in cardiac disease .

:*I_to1 density is significantly lower in the cells of a failing heart in comparison to the cells of a healthy heart.{{cite journal | vauthors = Beuckelmann DJ, Näbauer M, Erdmann E | title = Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure | journal = Circulation Research | volume = 73 | issue = 2 | pages = 379–385 | date = August 1993 | pmid = 8330380 | doi = 10.1161/01.RES.73.2.379 | doi-access = free }}

:*There is correlation between decreased I_to1 density and atrial fibrillation.{{cite journal | vauthors = Brandt MC, Priebe L, Böhle T, Südkamp M, Beuckelmann DJ | title = The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation | journal = Journal of Molecular and Cellular Cardiology | volume = 32 | issue = 10 | pages = 1885–1896 | date = October 2000 | pmid = 11013132 | doi = 10.1006/jmcc.2000.1221 }}

:*I_to activation is inhibited by thyrotropin (TSH).{{cite journal | vauthors = Alonso H, Fernández-Ruocco J, Gallego M, Malagueta-Vieira LL, Rodríguez-de-Yurre A, Medei E, Casis O | title = Thyroid stimulating hormone directly modulates cardiac electrical activity | journal = Journal of Molecular and Cellular Cardiology | volume = 89 | issue = Pt B | pages = 280–286 | date = December 2015 | pmid = 26497403 | doi = 10.1016/j.yjmcc.2015.10.019 | doi-access = free }} This mechanisms may be one of the reasons for the observation that both bradycardia and atrial fibrillation are common in hypothyroidism.{{cite journal | vauthors = Müller P, Leow MK, Dietrich JW | title = Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence | journal = Frontiers in Cardiovascular Medicine | volume = 9 | pages = 942971 | date = 15 August 2022 | pmid = 36046184 | pmc = 9420854 | doi = 10.3389/fcvm.2022.942971 | doi-access = free }}{{cite journal | vauthors = Zhang Y, Dedkov EI, Teplitsky D, Weltman NY, Pol CJ, Rajagopalan V, Lee B, Gerdes AM | title = Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats | journal = Circulation: Arrhythmia and Electrophysiology | volume = 6 | issue = 5 | pages = 952–959 | date = October 2013 | pmid = 24036190 | pmc = 3973490 | doi = 10.1161/CIRCEP.113.000502 }}{{cite journal | vauthors = Kolettis TM, Tsatsoulis A | title = Subclinical Hypothyroidism: An Overlooked Cause of Atrial Fibrillation? | journal = Journal of Atrial Fibrillation | volume = 5 | issue = 4 | pages = 710 | date = December 2012 | pmid = 28496796 | pmc = 5153160 | doi = 10.4022/jafib.710 | doi-broken-date = 1 November 2024 }}

• An increase in the I_to1 density caused by a mutation in Kv4.3 can be a cause of Brugada Syndrome.{{cite journal | vauthors = Giudicessi JR, Ye D, Tester DJ, Crotti L, Mugione A, Nesterenko VV, Albertson RM, Antzelevitch C, Schwartz PJ, Ackerman MJ | title = Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome | journal = Heart Rhythm | volume = 8 | issue = 7 | pages = 1024–1032 | date = July 2011 | pmid = 21349352 | pmc = 3150551 | doi = 10.1016/j.hrthm.2011.02.021 }}

{{reflist|30em}}

Category:Electrophysiology

Category:Cardiac electrophysiology