Constitutive BDNF/TrkB Signaling Is Required for Normal Cardiac Contraction and Relaxation
BDNF and its associated tropomyosin-related kinase receptor B (TrkB) nurture vessels and nerves serving the heart. However, the direct effect of BDNF/TrkB signaling on the myocardium is poorly understood. Here we report that cardiac-specific TrkB knockout mice (TrkB-/-) display impaired cardiac contraction and relaxation, showing that BDNF/TrkB signaling acts constitutively to sustain in vivo myocardial performance. BDNF enhances normal cardiomyocyte Ca2+ cycling, contractility, and relaxation via Ca2+/calmodulindependent protein kinase II (CaMKII). Conversely, failing myocytes, which have increased truncated TrkB lacking tyrosine kinase activity and chronically activated CaMKII, are insensitive to BDNF. Thus, BDNF/TrkB signaling represents a previously unidentified pathway by which the peripheral nervous system directly and tonically influences myocardial function in parallel with β-adrenergic control. Deficits in this system are likely additional contributors to acute and chronic cardiac dysfunction. BDNF TrkB receptorcardiac contractility/relaxation CaMKII neurotrophins We are grateful to Dr. David D. Ginty for providing us with TrkBF616A and TrkB conditional knockout mice.
Feng, Ning; Huke, Sabine; Zhua, Guangshuo; Tocchetti, Carlo G.; Shi, Sa; Aiba, Takeshi; Kaludercice, Nina; Hoover, Donald B.; Beckg, Sarah E.; Mankowskig, Joseph L.; Tomaselli, Gordon F.; Bersh, Donald M.; Kassa, David A.; and Paoloccia, Nazareno. 2015. Constitutive BDNF/TrkB Signaling Is Required for Normal Cardiac Contraction and Relaxation. Proceedings of the National Academy of Sciences of the United States of America. Vol.112(6). 1880-1885. https://doi.org/10.1073/pnas.1417949112 PMID: 25583515 ISSN: 0027-8424