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

Ning Feng, Sabine Huke, Guangshuo Zhua, Carlo G. Tocchettic, Sa Shi, Takeshi Aiba, Nina Kaludercice, Donald B. Hooverf, Sarah E. Beckg, Joseph L. Mankowskig, Gordon F. Tomaselli, Donald M. Bersh, David A. Kassa, Nazareno Paoloccia

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)1880-1885
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number6
DOIs
StatePublished - Feb 10 2015
Externally publishedYes

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Brain-Derived Neurotrophic Factor
Protein Kinases
Knockout Mice
tropomyosin kinase
Peripheral Nervous System
Nerve Growth Factors
Cardiac Myocytes
Adrenergic Agents
Protein-Tyrosine Kinases
Muscle Cells
Myocardium

ASJC Scopus subject areas

  • General

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Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation. / Feng, Ning; Huke, Sabine; Zhua, Guangshuo; Tocchettic, Carlo G.; Shi, Sa; Aiba, Takeshi; Kaludercice, Nina; Hooverf, Donald B.; Beckg, Sarah E.; Mankowskig, Joseph L.; Tomaselli, Gordon F.; Bersh, Donald M.; Kassa, David A.; Paoloccia, Nazareno.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, No. 6, 10.02.2015, p. 1880-1885.

Research output: Contribution to journalArticle

Feng, N, Huke, S, Zhua, G, Tocchettic, CG, Shi, S, Aiba, T, Kaludercice, N, Hooverf, DB, Beckg, SE, Mankowskig, JL, Tomaselli, GF, Bersh, DM, Kassa, DA & Paoloccia, N 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, no. 6, pp. 1880-1885. https://doi.org/10.1073/pnas.1417949112
Feng, Ning ; Huke, Sabine ; Zhua, Guangshuo ; Tocchettic, Carlo G. ; Shi, Sa ; Aiba, Takeshi ; Kaludercice, Nina ; Hooverf, Donald B. ; Beckg, Sarah E. ; Mankowskig, Joseph L. ; Tomaselli, Gordon F. ; Bersh, Donald M. ; Kassa, David A. ; Paoloccia, Nazareno. / Constitutive BDNF/TrkB signaling is required for normal cardiac contraction and relaxation. In: Proceedings of the National Academy of Sciences of the United States of America. 2015 ; Vol. 112, No. 6. pp. 1880-1885.
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