Glutamate-induced currents reveal three functionally distinct NMDA receptor populations in rat dorsal horn - effects of peripheral nerve lesion and inflammation.
The importance of the N-methyl-D-aspartate (NMDA) receptor in various painful conditions is well established. The effects of peripheral nerve lesion or joint inflammation, as models of different pain states, on NMDA receptor-mediated currents and NMDA receptor subunit mRNA expression were therefore studied in acutely dissociated neurones from the rat spinal cord dorsal horn. In the neuronal population from control rats, all four NR2 subunits and both NR1 splice variants assayed were detected. A majority of neurones expressed mRNA for more than one NR2 subunit, and some neurones expressed all four NR2 subunits as well as both NR1 splice variants. The NR2B subunit was the most commonly expressed, while the NR2C was the rarest. Following nerve lesion, fewer neurones expressed NR2A compared to the control. The dose-response curve for glutamate-evoked NMDA receptor-mediated currents in the neurones was best described by a three-component fit, suggesting that three functionally distinct NMDA receptor populations are present in the dorsal horn. Minor changes in the dose-response curve after nerve lesion could not be ascribed with certainty to the lesion. Changes in other parameters of NMDA receptor-mediated currents were observed neither after nerve lesion nor after joint inflammation. In summary, the present work demonstrates that single dorsal horn neurones express mRNA for several NMDA receptor subunits. The glutamate dose-response curves indicate that there are three major types of NMDA receptors present in dorsal horn neurones. We also report a reduced expression of NR2A following peripheral nerve lesion.
Karlsson
U
U
AstraZeneca, R&D Södertälje, Novum, S-141 57 Huddinge, Sweden. urban.karlsson@astrazeneca.com
Sjödin
J
J
Angeby Möller
K
K
Johansson
S
S
Wikström
L
L
Näsström
J
J
D000818:Animals; D018929:Cell Culture Techniques; D004594:Electrophysiology; D005620:Freund's Adjuvant; D018698:Glutamic Acid / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D059348:Peripheral Nerve Injuries; D020671:Posterior Horn Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C409466:NR1 NMDA receptor; C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D005620:Freund's Adjuvant