TRPC5 channel is the mediator of neurotrophin-3 in regulating dendritic growth via CaMKIIα in rat hippocampal neurons.

Neurotrophin-3 (NT-3) plays numerous important roles in the CNS and the elevation of intracellular Ca2+ ([Ca2+](i)) is critical for these functions of NT-3. However, the mechanism by which NT-3 induces [Ca2+](i) elevation remains largely unknown. Here, we found that transient receptor potential canonical (TRPC) 5 protein and TrkC, the NT-3 receptor, exhibited a similar temporal expression in rat hippocampus and cellular colocalization in hippocampal neurons. Stimulation of the neurons by NT-3 induced a nonselective cation conductance and PLC gamma-dependent [Ca2+](i) elevation, which were both blocked when TRPC5, but not TRPC6 channels, were inhibited. Moreover, the Ca2+ influx through TRPC5 induced by NT-3 inhibited the neuronal dendritic growth through activation of calmodulin-dependent kinase (CaMK) II alpha. In contrast, the Ca2+ influx through TRPC6 induced by NT-4 promoted the dendritic growth. Thus, TRPC5 acts as a novel and specific mediator for NT-3 to regulate dendrite development through CaMKII alpha.