Research Papers:

Kv4.3 expression reverses ICa remodeling in ventricular myocytes of heart failure

Jun Cheng, Jianlei Cao, Xingchen Jiang, Lin Xu and Yanggan Wang _

PDF  |  HTML  |  How to cite

Oncotarget. 2017; 8:104037-104045. https://doi.org/10.18632/oncotarget.21956

Metrics: PDF 1193 views  |   HTML 1564 views  |   ?  


Jun Cheng1,*, Jianlei Cao1,*, Xingchen Jiang1,*, Lin Xu3 and Yanggan Wang1,2

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

2Medical Research Institute of Wuhan University, Wuhan University, Wuhan 430071, China

3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, China

*These authors have contributed equally to this work

Correspondence to:

Yanggan Wang, email: [email protected]

Keywords: L-type calcium current; Kv4.3; CaMKII; myocytes; heart failure

Received: July 04, 2017     Accepted: September 25, 2017     Published: October 23, 2017


Background: Ca2+/calmodulin-dependent protein kinase II (CaMKII)-dependent L-type calcium channel (LTCC) current (ICa) remodeling is an important contributor to the disruption of calcium homeostasis in heart failure (HF). We have reported that Kv4.3 proteins play an important role in delicate regulation of the membrane-associated CaMKII activity in ventricular myocytes. Here, we investigated the effect of in vivo Kv4.3 expression on ICa in HF left ventricular (LV) myocytes.

Results: Kv4.3 expression reduced overall CaMKII autophosphorylation with much greater reduction in the membrane compartmentalized CaMKII activity. ICa density in subepicardial (SEP) and subendocardial (SEN) myocytes was proportionately reduced, without changing the transmural gradient. While the time course of ICa decay was hastened, the voltage-dependence of ICa activation and inactivation, however, remained unchanged. ICa recovery from inactivation was significantly accelerated. In line with the partial inhibition of CaMKII, the frequency-dependent Ca2+-induced ICa facilitation was recovered in the HF myocytes transfected with Kv4.3.

Materials and Methods: Pressure-overload HF was induced by thoracic aortic banding. Kv4.3 expression was achieved by Ad-Kv4.3 injection in the LV myocardium. ICa was recorded in dissociated SEP and SEN myocytes using whole-cell patch clamp method.

Conclusions: Kv4.3 expression in HF ventricle can effectively reverse ICa remodeling via inhibition of the membrane-associated CaMKII, pointing to Kv4.3 restoration as a potential therapeutic approach for the disordered calcium regulation in HF.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 21956