- Feng, Ning;
- Huke, Sabine;
- Zhu, Guangshuo;
- Tocchetti, Carlo G;
- Shi, Sa;
- Aiba, Takeshi;
- Kaludercic, Nina;
- Hoover, Donald B;
- Beck, Sarah E;
- Mankowski, Joseph L;
- Tomaselli, Gordon F;
- Bers, Donald M;
- Kass, David A;
- Paolocci, Nazareno
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 Ca(2+) cycling, contractility, and relaxation via Ca(2+)/calmodulin-dependent 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.