caa a22 4500 605478872 CHVBK 20210128100407.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s10741-015-9474-y doi (NATIONALLICENCE)springer-10.1007/s10741-015-9474-y Transient outward potassium channel: a heart failure mediator [Elektronische Daten] [Qianwen He, Ying Feng, Yanggan Wang] Transient outward K+ current (I to) plays a crucial role in shaping the early phase of repolarization and setting the plateau voltage level of action potential. As a result, it extensively affects membrane current flow in the plateau window. A great body of evidence illustrates a transmural gradient of I to within ventricular wall with much higher density in epicardial than endocardial myocytes, which is important for the physiological ventricular repolarization. In heart failure (HF), this gradient is diminished due to a greater reduction of I to in epicardial myocytes. This attenuates the transmural gradient of early repolarization, facilitating conduction of abnormal impulses originated in the epicardium. In addition, I to reduction prolongs action potential duration and increases intercellular Ca2+, thus affecting Ca2+ handling and the excitation-contraction coupling. Furthermore, increased intercellular Ca2+ could activate CaMKII and calcineurin whose role in cardiac hypertrophy and HF development has been well established. Based on the impact of I to reduction on electrical activity, signal conduction, calcium handling and cardiac function, restoration of I to is likely a potential therapeutic strategy for HF. In this review, we summarize the physiological and pathological role of cardiac I to channel and the potential impact of I to restoration on HF therapy with an emphasis of recent novel findings. Springer Science+Business Media New York, 2015 Transient outward potassium current nationallicence Heart failure nationallicence Ca2+ handling nationallicence CaMKII nationallicence Calcineurin nationallicence He Qianwen Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut Feng Ying Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut Wang Yanggan Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut Heart Failure Reviews Springer US; http://www.springer-ny.com 20/3(2015-05-01), 349-362 1382-4147 20:3<349 2015 20 10741 https://doi.org/10.1007/s10741-015-9474-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10741-015-9474-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- He Qianwen Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut NATIONALLICENCE 700 1- Feng Ying Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut NATIONALLICENCE 700 1- Wang Yanggan Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, 430071, Wuhan, China aut NATIONALLICENCE 773 0- Heart Failure Reviews Springer US; http://www.springer-ny.com 20/3(2015-05-01), 349-362 1382-4147 20:3<349 2015 20 10741