Biology:Cardiac transient outward potassium current
The cardiac transient outward potassium current (referred to as Ito1 or Ito[1]) is one of the ion currents across the cell membrane of heart muscle cells. It is responsible for the (brief) repolarizing phase 1 of the cardiac action potential (which succeeds depolarisation, and precedes the plateau phase).[2] The Ito is produced by movement of positively charged potassium (K+) ions from the intracellular into the extracellular space. It exhibits rapid activation and inactivation.[3] Ito1 is complemented with Ito2 resulting from Cl− ions to form the transient outward current Ito. The Ito1 is generated by voltage-gated K+ channels Kv1.4, Kv4.2, and (especially) Kv4.3; these channels undergo ball-and-chain inactivation to terminate the current.[3]
It occurs in atrial, ventricular, and conduction system cells. In ventricular myocardium, it is more potent in the epicardium than the endocardium; this transmural Ito1 gradient underlies the J wave ECG finding.[3]
Role in disease
- Reduction in Ito1 density is associated with prolonged action potentials and is a common finding in cardiac disease.[4]
- Ito1 density is significantly lower in the cells of a failing heart in comparison to the cells of a healthy heart.[5]
- There is correlation between decreased Ito1 density and atrial fibrillation.[6]
- Ito activation is inhibited by thyrotropin (TSH).[7] This mechanisms may be one of the reasons for the observation that both bradycardia and atrial fibrillation are common in hypothyroidism.[8][9][10]
- An increase in the Ito1 density caused by a mutation in Kv4.3 can be a cause of Brugada Syndrome.[11]
References
- ↑ "Molecular determinants of cardiac transient outward potassium current (I(to)) expression and regulation". Journal of Molecular and Cellular Cardiology 48 (1): 12–25. January 2010. doi:10.1016/j.yjmcc.2009.07.013. PMID 19619557.
- ↑ Greger, Rainer; Windhorst, Uwe (1996). Comprehensive Human Physiology: From Cellular Mechanisms to Integration. Berlin, Heidelberg: Springer. p. 1828. ISBN 978-3-642-60946-6.
- ↑ 3.0 3.1 3.2 Asirvatham, Samuel J., ed (2014). Mayo Clinic Electrophysiology Manual. Oxford: Mayo Clinic Scientific Press/Oxford University Press. p. 174. ISBN 978-0-19-933041-6.
- ↑ "The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium". Journal of Molecular and Cellular Cardiology 33 (5): 851–872. May 2001. doi:10.1006/jmcc.2001.1376. PMID 11343410.
- ↑ "Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure". Circulation Research 73 (2): 379–385. August 1993. doi:10.1161/01.RES.73.2.379. PMID 8330380.
- ↑ "The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation". Journal of Molecular and Cellular Cardiology 32 (10): 1885–1896. October 2000. doi:10.1006/jmcc.2000.1221. PMID 11013132.
- ↑ "Thyroid stimulating hormone directly modulates cardiac electrical activity". Journal of Molecular and Cellular Cardiology 89 (Pt B): 280–286. December 2015. doi:10.1016/j.yjmcc.2015.10.019. PMID 26497403.
- ↑ "Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence". Frontiers in Cardiovascular Medicine 9. 15 August 2022. doi:10.3389/fcvm.2022.942971. PMID 36046184.
- ↑ "Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats". Circulation: Arrhythmia and Electrophysiology 6 (5): 952–959. October 2013. doi:10.1161/CIRCEP.113.000502. PMID 24036190.
- ↑ "Subclinical Hypothyroidism: An Overlooked Cause of Atrial Fibrillation?". Journal of Atrial Fibrillation 5 (4): 710. December 2012. doi:10.4022/jafib.710. PMID 28496796.
- ↑ "Transient outward current (I(to)) gain-of-function mutations in the KCND3-encoded Kv4.3 potassium channel and Brugada syndrome". Heart Rhythm 8 (7): 1024–1032. July 2011. doi:10.1016/j.hrthm.2011.02.021. PMID 21349352.
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