Trpc Channels Promote Survival Of Cerebellar Granule Cells And Neurons Involved In Bdnf-mediated Axon Guidance

Channels formed by the TRP family of proteins serve for a variety of physiologicalfunctions. Here we report that two members of the TRPC subfamily, TRPC3 orTRPC6, promotes survival of cerebellar granule neurons (CGNs) in the rat brain andprotects cultured CGNs against serum-deprivation (SD)-induced cell death.Knock-down of TRPC3/6 with RNAi induced CGN apoptosis in neonatal ratcerebellum and this effect was rescued by over-expressing either TRPC3 or TRPC6.In CGN cultures, blocking TRPC channels or down-regulating TRPC3/6 expressionsuppressed BDNF-dependent neuronal protection, BDNF-triggered ERK and CREBphosphorylation. Notably, over-expressing TRPC3/6 prevented SD-induced cell deathand this effect could be blocked by dominant negative form of CREB. Furthermore,inhibition or down-regulation of PLC/IP3 receptor suppressed BDNF-dependentprotection on CGNs. Thus, our findings provide in vivo and in vitro evidence for acritical role of TRPC channels in promoting neuronal survival.