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

Authors: Sun, B  Sheng, Y  Huo, R  Hu, CW  Lu, J  Li, SL  Liu, X  Wang, YC  Dong, DL 
Citation: Sun B, etal., Biochem Biophys Res Commun. 2013 Jul 12;436(4):591-4. doi: 10.1016/j.bbrc.2013.05.113. Epub 2013 Jun 6.
Pubmed: (View Article at PubMed) PMID:23747723
DOI: Full-text: DOI:10.1016/j.bbrc.2013.05.113

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.

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CRRD Object Information
CRRD ID: 8847123
Created: 2014-08-14
Species: All species
Last Modified: 2014-08-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.