Satellite glia cells in dorsal root ganglia express functional NMDA receptors.

Satellite glia cells (SGCs), within the dorsal root ganglia (DRG), surround the somata of most sensory neurons. SGCs have been shown to interact with sensory neurons and appear to be involved in the processing of afferent information. We found that in rat DRG various N-methyl-D-aspartate receptor (NMDAr) subunits were expressed in SGCs in intact ganglia and in vitro. In culture, when SGCs were exposed to brief pulses of NMDA they evoked transient increases in cytoplasmic calcium that were inhibited by specific NMDA blockers (MK-801, AP5) while they were Mg²âº insensitive indicating that SGCs express functional NMDAr. The percentage of NMDA responsive SGCs was similar in mixed- (SGCs plus neurons) and SGC-enriched cultures. The pattern of the magnitude changes of the NMDA-evoked response was similar in SGCs and DRG neurons when they were in close proximity, suggesting that the NMDA response of SGCs and DRG neurons is modulated by their interactions. Treating the cultures with nerve growth factor, and/or prostaglandin E2 did not alter the percentage of SGCs that responded to NMDA. Since glutamate appears to be released within the DRG, the detection of functional NMDAr in SGCs suggests that their NMDAr activity could contribute to the interactions between neurons and SGCs. In summary we demonstrated for the first time that SGCs express functional NMDAr.

The N-methyl-D-aspartate-evoked cytoplasmic calcium increase in adult rat dorsal root ganglion neuronal somata was potentiated by substance P pretreatment in a protein kinase C-dependent manner.

The involvement of substance P (SP) in neuronal sensitization through the activation of the neurokinin-1-receptor (NK1r) in postsynaptic dorsal horn neurons has been well established. In contrast, the role of SP and NK1r in primary sensory dorsal root ganglion (DRG) neurons, in particular in the soma, is not well understood. In this study, we evaluated whether SP modulated the NMDA-evoked transient increase in cytoplasmic Ca2+ ([Ca2+]cyt) in the soma of dissociated adult DRG neurons. Cultures were treated with nerve growth factor (NGF), prostaglandin E2 (PGE2) or both NGF+PGE2. Treatment with NGF+PGE2 increased the percentage of N-methyl-D-aspartate (NMDA) responsive neurons. There was no correlation between the percentage of NMDA responsive neurons and the level of expression of the NR1 and NR2B subunits of the NMDA receptor or of the NK1r. Pretreatment with SP did not alter the percentage of NMDA responsive neurons; while it potentiated the NMDA-evoked [Ca2+]cyt transient by increasing its magnitude and by prolonging the period during which small- and some medium-sized neurons remained NMDA responsive. The SP-mediated potentiation was blocked by the SP-antagonist ([D-Pro4, D-Trp7,9]-SP (4-11)) and by the protein kinase C (PKC) blocker bisindolylmaleimide I (BIM); and correlated with the phosphorylation of PKCε. The Nk1r agonist [Sar9, Met(O2)11]-SP (SarMet-SP) also potentiated the NMDA-evoked [Ca2+]cyt transient. Exposure to SP or SarMet-SP produced a rapid increase in the labeling of phosphorylated-PKCε. In none of the conditions we detected phosphorylation of the NR2B subunit at Ser-1303. Phosphorylation of the NR2B subunit at Tyr1472 was enhanced to a similar extent in cells exposed to NMDA, SP or NMDA+SP, and that enhancement was blocked by BIM. Our findings suggest that NGF and PGE2 may contribute to the injury-evoked sensitization of DRG neurons in part by enhancing their NMDA-evoked [Ca2+]cyt transient in all sized DRG neurons; and that SP may further contribute to the DRG sensitization by enhancing and prolonging the NMDA-evoked increase in [Ca2+]cyt in small- and medium-sized DRG neurons.