Bone morphogenetic protein-4 contributes to the down-regulation of Kv4.3 K+ channels in pathological cardiac hypertrophy.

Abstract

Kv4.3 K(+) channels contributing to Ito are involved in the repolarization of cardiac action potential. Kv4.3 K(+) channels decrease in pathological cardiac hypertrophy, but the mechanism remains unclear. Our previous study found that the expression of bone morphogenetic protein 4 (BMP4) increased in pressure-overload and Ang II constant infusion induced cardiac hypertrophy. Since the downregulation of Kv4.3 K(+) channels and the upregulation of BMP4 simultaneously occur in pathological cardiac hypertrophy, we hypothesize that the up-regulated BMP4 would contribute to the downregulation of Kv4.3 K(+) channels in cardiac hypertrophy. We found that BMP4 treatment reduced Kv4.3 but not Kv4.2 and Kv1.4 K(+) channel protein expression, and BMP4-induced decrease of Kv4.3 K(+) channel protein expression was reversed by BMP4 inhibitor noggin and DMH1 in cultured cardiomyocytes in vitro. BMP4-induced decrease of Kv4.3 K(+) channel protein expression was also reversed by the NADPH oxidase inhibitor apocynin and the radical scavenger tempol. In in vivo transverse aortic constriction (TAC)-induced cardiac hypertrophy, constant infusion of DMH1 completely rescued TAC-induced down-regulation of Kv4.3 K(+) channel protein expression. We conclude that BMP4 contributes to the downregulation of Kv4.3 K(+) channels in pathological cardiac hypertrophy and the underlying mechanism might be through increasing ROS production.

• Authors: Bo Sun, Yue Sheng, Rong Huo, Chao-Wei Hu, Jing Lu, Shan-Liang Li, Xiao Liu, Yu-Chun Wang, De-Li Dong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 436 Issue 4 Pg. 591-4 (Jul 12 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23747723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Bmp4 protein, rat
• Bone Morphogenetic Protein 4
• DNA Primers
• Shal Potassium Channels

Topics

• Animals
• Base Sequence
• Bone Morphogenetic Protein 4 (physiology)
• Cardiomegaly (physiopathology)
• DNA Primers
• Down-Regulation (physiology)
• Humans
• Rats
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Shal Potassium Channels (physiology)