Brain‐derived Neurotrophic Factor (BDNF) Directly Modulates Cardiac Ventricular Myocyte Function

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin that affects myocardial function via neurally‐ or vascular‐mediated mechanisms. Whether BDNF directly influences myocyte contraction/relaxation is unknown. Results By immunohistochemistry and immunoblot, here we show that BDNF‐selective tropomyosine kinase receptor B (trkB) are on the sarcolemma of rodent ventricular myocytes (VM). BDNF superfusion in these cells elicits positive inotropy. Both %fractional shortening and whole Ca 2+ transient amplitude increase after BDNF, without altering diastolic Ca 2+ levels. BDNF enhances SR‐Ca 2+ fractional release without altering SR‐Ca 2+ load. TrkB receptors are central to these actions because BDNF stimulation is lost in TrkB −/− myocytes. BDNF inotropy involves CaMKII activation. Indeed, after BDNF cardiac CaMKII was phosphorylated while inhibiting this kinase via KN‐93 fully offsets BDNF inotropy. Downstream targets of BDNF‐CaMKII signaling pathways are L‐type Ca 2+ channels because BDNF increases their currents. Moreover, myocyte incubation with BDNF augments phosphorylation of ryanodine receptors at CaMKII site, but not at the PKA site, likely accounting for BDNF enhancement of SR Ca 2+ fractional release. Conclusions We show for the first time that BDNF directly modulates myocardial function, highlighting a new way for the peripheral nervous system to govern cardiac function.