The potential role of Kv4.3 K+ channel in heart hypertrophy

作者：Huo Rong; Sheng Yue; Guo Wen Ting; Dong De Li^*

来源：Channels, 2014, 8(3): 203-209.

DOI：10.4161/chan.28972

• Kv4.3 K+ channel
• heart hypertrophy
• heart failure
• CaMKII

Transient outward K+ current (I-to) plays a crucial role in the early phase of cardiac action potential repolarization. Kv4.3 K+ channel is an important component of I-to. The function and expression of Kv4.3 K+ channel decrease in variety of heart diseases, especially in heart hypertrophy/heart failure. In this review, we summarized the changes of cardiac Kv4.3 K+ channel in heart diseases and discussed the potential role of Kv4.3 K+ channel in heart hypertrophy/heart failure. In heart hypertrophy/heart failure of mice and rats, downregulation of Kv4.3 K+ channel leads to prolongation of action potential duration (APD), which is associated with increased [Ca2+](i), activation of calcineurin and heart hypertrophy/heart failure. However, in canine and human, Kv4.3 K+ channel does not play a major role in setting cardiac APD. So, in addition to Kv4.3 K+ channel/APD/[Ca2+](i) pathway, there exits another mechanism of Kv4.3 K+ channel in heart hypertrophy and heart failure: downregulation of Kv4.3 K+ channels leads to CaMKII dissociation from Kv4.3-CaMKII complex and subsequent activation of the dissociated CaMKII, which induces heart hypertrophy/heart failure. Upregulation of Kv4.3 K+ channel inhibits CaMKII activation and its related harmful consequences. We put forward a new point-of-view that Kv4.3 K+ channel is involved in heart hypertrophy/heart failure independently of its electric function, and drugs inhibiting or upregulating Kv4.3 K+ channel might be potentially harmful or beneficial to hearts through CaMKII.

• 出版日期2014-6
• 单位哈尔滨医科大学