The potential role of Kv4.3 K+ channel in heart  hypertrophy.
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. Int his 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, down regulation of Kv4.3 K(+) channel leads to prolongation of action potential duration (APD), which is associated with increased [Ca(2+)](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/[Ca(2+)](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 Kv4.3K(+) 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.
Rong
R
Huo
Yue
Y
Sheng
Wen-Ting
WT
Guo
De-Li
DL
Dong
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D051381:Rats; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*
D051672:Shal Potassium Channels; D002118:Calcium