Antagonism of mGlu receptors and potentiation of EPSCs at rat spinal motoneurones in vitro.
The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8) was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no significant effect on the depressant potency of AP4. Under control conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary afferent terminals presynaptic to motoneurones as well as in pathways via interneurones. These results are consistent with the presence of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These receptors appear to be activated by interstitial glutamate tonically present in the present preparations.
Cao
C Q
CQ
Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
Tse
H W
HW
Jane
D E
DE
Evans
R H
RH
Headley
P M
PM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D018094:Receptors, Metabotropic Glutamate; D005998:Glycine