A COMPARISON OF THE EFFECTS OF SELECTIVE METABOTROPIC GLUTAMATE-RECEPTOR AGONISTS ON SYNAPTICALLY EVOKED WHOLE-CELL CURRENTS OF RAT SPINAL VENTRAL HORN NEURONS IN-VITRO

被引:35
作者
CAO, CQ
EVANS, RH
HEADLEY, PM
UDVARHELYI, PM
机构
[1] UNIV BRISTOL,SCH MED SCI,DEPT PHARMACOL,BRISTOL BS8 1TD,AVON,ENGLAND
[2] UNIV BRISTOL,SCH MED SCI,DEPT PHYSIOL,BRISTOL BS8 1TD,AVON,ENGLAND
基金
英国惠康基金;
关键词
SPINAL NEURONS; METABOTROPIC; GLUTAMATE RECEPTOR;
D O I
10.1111/j.1476-5381.1995.tb16639.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Whole cell synaptic currents were recorded under voltage clamp from a total of 54 ventral horn neurones held near to their resting potential by the patch clamp technique in immature rat spinal cord preparations in vitro. Twenty eight neurones were identified, by antidromic invasion from ventral roots, as motoneurones. Excitatory postsynaptic currents (e.p.s.cs) of peak amplitude -480 pA +/- 66 s.e.mean and -829 +/- 124 pA were evoked respectively from the unidentified ventral horn neurones and the motoneurones in response to maximal activation of the segmental dorsal root. 2 The e.p.s.cs were depressed reversibly by the metabotropic glutamate agonists 1S3S-1-aminocyclopentane-1,3-dicarboxylate (1S3S-ACPD) (EC(50) 17.1 mu M +/- 0.3 s.e.mean, n = 14) and L-2-amino-4-phosphonobutanoate (L-AP4) (EC(50) = 2.19 +/- 0.19 mu M, n = 15). Since both agonists independently produced more than 90% depression it is likely that the receptors that mediate their effects are present on the same presynaptic terminals. 3 When the Mg2(+) concentration was raised From 0.75 mM to 2.75 mM together with the addition of 50 mu M D-2-amino-5-phosphonopentanoate (AP5), a treatment which would increase the proportion of monosynaptic component in the e.p.s.c. the concentration-effect plots for both IS3S-ACPD (EC(50) 1.95 +/- 0.4 mu m, n = 8) and L-AP4 (EC(50) 0.55 +/- 0.20 mu M, n = 7) were shifted to the left, suggesting that monosynaptic e.p.cs of primary afferents to ventral horn neurones are more susceptible to L-AP4 and 1S3S-ACPD than are other synapses in polysynaptic pathways. 4 1S3S-ACPD (20 and 50 mu M) also caused mean sustained inward currents of 95 +/- 31 pA (n = 6) and 248 +/- 49 pA (n = 10) respectively. In the combined presence of AP5 (50 mu M) and Mg2+ (2.75 mM) the mean response to 50 mu M 1S3S-ACPD was reduced to 106 +/- 18 pA (n = 4). In the presence of tetrodotoxin (1 mu M) the corresponding value was 48 +/- 6 pA (n = 4). Similar sustained inward currents produced by N-methyl-D-aspartate (NMDA) were almost abolished to < 10 pA in the presence of AP5 and 2.75 mM Mg2+. In the presence of tetrodotoxin the maximum inward current produced by NMDA was undiminished. Thus a large component of the excitatory action of 1S3S-ACPD was mediated at non-NMDA receptors both directly at the patch-clamped neurones and indirectly by synaptic relay.
引用
收藏
页码:1469 / 1474
页数:6
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