Differential gene expression of neonatal and adult DRG neurons correlates with the differential sensitization of TRPV1 responses to nerve growth factor.

摘要

Cultures of neonatal and adult dorsal root ganglion (DRG) neurons are commonly used in in vitro models to study the ion channels and signaling events associated with peripheral sensation under various conditions. Differential responsiveness between neonatal and adult DRG neurons to physiological or pathological stimuli suggests potential differences in their gene expression profiles. We performed a microarray analysis of cultured adult and neonatal rat DRG neurons, which revealed distinct gene expression profiles especially of ion channels and signaling molecules at the genomic level. For example, Ca(2+)-stimulated adenylyl cyclase (AC) isoforms AC3 and AC8, PKCdelta and CaMKIIalpha, the voltage-gated sodium channel beta1 and beta4, and potassium channels K(v)1.1, K(v)3.2, K(v)4.1, K(v)9.1, K(v)9.3, K(ir)3.4, K(ir)7.1, K(2P)1.1/TWIK-1 had significantly higher mRNA expression in adult rat DRG neurons, while Ca(2+)-inhibited AC5 and AC6, sodium channel Na(v)1.3 alpha subunit, potassium channels K(ir)6.1, K(2P)10.1/TREK-2, calcium channel Ca(v)2.2 alpha1 subunit, and its auxiliary subunits beta1 and beta3 were conversely down regulated in adult neurons. Importantly, higher adult neuron expression of ERK1/2, PI3K/P110alpha, but not of TRPV1 and TrkA, was found and confirmed by PCR and western blot. These latter findings are consistent with the key role of ERK and PI3K signaling in sensitization of TRPV1 by NGF and may explain our previously published observation that adult, but not neonatal, rat DRG neurons are sensitized by NGF.