title: Transient outward potassium channel: a heart failure mediator.
abstract: Transient outward K(+) current (Ito) 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 Ca(2+), thus affecting Ca(2+) handling and the excitation-contraction coupling. Furthermore, increased intercellular Ca(2+) 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.
authors: Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China.
authors: Qianwen
authors: Q
authors: He
authors: Ying
authors: Y
authors: Feng
authors: Yanggan
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000502:physiology; D018740:Genetic Heterogeneity; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism; D010496:Pericardium / Q000503:physiopathology; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D015221:Potassium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019703:Calcineurin; D002118:Calcium
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