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Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation.


ABSTRACT: 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 ?-adrenergic control. Deficits in this system are likely additional contributors to acute and chronic cardiac dysfunction.

SUBMITTER: Feng N 

PROVIDER: S-EPMC4330748 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation.

Feng Ning N   Huke Sabine S   Zhu Guangshuo G   Tocchetti Carlo G CG   Shi Sa S   Aiba Takeshi T   Kaludercic Nina N   Hoover Donald B DB   Beck Sarah E SE   Mankowski Joseph L JL   Tomaselli Gordon F GF   Bers Donald M DM   Kass David A DA   Paolocci Nazareno N  

Proceedings of the National Academy of Sciences of the United States of America 20150112 6


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 relaxati  ...[more]

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