BDNF conveys its activity by binding to two classes of receptors, a member of the Trk receptor tyrosine kinase family (TrkB) and the pan-neurotrophin receptor p75NTR. Binding of BDNF to the TrkB receptor triggers ligand-induced dimerization and autophosphorylation of tyrosine residues. This activates various signaling cascades such the MAPK, PI3K and PLCγ pathways that are involved in cell growth, survival and differentiation of neurons in the central and peripheral nervous system. Interestingly, recent evidence suggests that BDNF may influence target cell function via ion channel modulation. Ion channel activity in the target cells can be modulated by a TrkB-mediated mechanism that has not yet been determined. BDNF is able to block both KV1.3 and AMPA-subtype glutamate ion channel currents in sensory neurons, while it can induce activation of the TRPC3 cation channel in neurons and of the NaV1.9 Na+ channel in hippocampal neurons. These newly recognized BDNF actions underlie its “rapid” neuronal functions that include changes in neuronal excitability, plasticity and synaptic transmission.
