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

Significance BDNF plays a key role in neuron development, survival, and function, with actions occurring through the stimulation of the tropomyosin-related kinase receptor B (TrkB) receptor. Whether BDNF/TrkB signaling has any physiologic role in governing myocardial function is unknown. Here we report that intact BDNF/TrkB signaling is required for the heart to fully contract and relax. These actions occur independently from and in addition to β-adrenergic influence. BDNF-induced enhancement of myocardial performance occurs via direct modulation of Ca 2+ cycling in a calmodulin-dependent protein kinase II-dependent manner. Thus, BDNF/TrkB signaling represents a previously unidentified way by which the peripheral nervous system controls cardiac muscle physiology. Our study suggests that loss or alterations in BDNF/TrkB stimulation may contribute to the pathogenesis of myocardial dysfunction in acute or chronic disease conditions.