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Transient outward potassium channel: a heart failure mediator

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Abstract

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.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China to Yanggan Wang [NSFC, Grant Nos. 81270304 and 81420108004].

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No conflicts of interest to disclose.

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  1. Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China

    Qianwen He, Ying Feng & Yanggan Wang

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  1. Qianwen He
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  2. Ying Feng
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  3. Yanggan Wang
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Correspondence to Yanggan Wang.

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He, Q., Feng, Y. & Wang, Y. Transient outward potassium channel: a heart failure mediator. Heart Fail Rev 20, 349–362 (2015). https://doi.org/10.1007/s10741-015-9474-y

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