scholarly journals ATP P2X Receptor-Mediated Enhancement of Glutamate Release and Evoked EPSCs in Dorsal Horn Neurons of the Rat Spinal Cord

2001 ◽  
Vol 21 (17) ◽  
pp. 6522-6531 ◽  
Author(s):  
Terumasa Nakatsuka ◽  
Jianguo G. Gu
2010 ◽  
Vol 6 ◽  
pp. 1744-8069-6-25 ◽  
Author(s):  
Stefan K Georgiev ◽  
Hidemasa Furue ◽  
Hiroshi Baba ◽  
Tatsuro Kohno

1991 ◽  
Vol 66 (6) ◽  
pp. 1941-1950 ◽  
Author(s):  
D. S. Magnuson ◽  
A. H. Dickenson

1. Extracellular recordings were made from 95 dorsal horn neurons in a sagittal slice preparation of rat spinal cord. Neurons were synaptically activated by electrical stimulation of the dorsal root entry zone (n = 72) or driven by pressure ejection of L-glutamate into the substantia gelatinosa (SG; n = 23). For the majority of neurons low-intensity electrical stimuli evoked a burst of spikes with short latency (early firing). An increase in the stimulus intensity evoked the early firing followed by a characteristic prolonged period of activity (late firing). 2. The patterns of synaptically induced activity observed from neurons located in the SG (n = 45) and in deeper laminae (n = 27) were similar. Early and late firing of both SG and deep neurons was reduced by the nonspecific excitatory amino acid antagonist kynurenate. Raising [Mg2+] in the superfusate to 5 from 2.0 mM selectively reduced the late firing of both SG and deep neurons. These findings suggest that fibers present in the dorsal root zone make excitatory amino acid-mediated synapses with dorsal horn neurons. 3. The majority of deep neurons showed reduced responses to electrical stimuli in the presence of morphine, mimicking the findings reported in vivo. Naloxone reversed morphine inhibitions or, when applied to morphine-naive slices, caused modest increases in the responses of some deep neurons. 4. Most neurons located in the SG had their responses enhanced by morphine (late firing: 86.5 +/- 19.6%, mean +/- SE) and were inhibited by naloxone (-78.3 +/- 22.7%). Morphine-induced enhancements often persisted long after the morphine had washed out of the bath. Inhibitions by naloxone, whether pre- or postmorphine, were short lived; and responses generally returned to either control or morphine-enhanced levels on washout of the naloxone. 5. The gamma-aminobutyric acid (GABA) antagonist bicuculline, applied to GABA-naive slices, caused an increase in response of SG neurons while slightly depressing activity of deep neurons. A tonic release or presence of endogenous GABA, affecting neurons that are inhibited by exogenously applied GABA, may be responsible for the observed action of bicuculline. 6. Intracellular recordings were made from a further 32 dorsal horn neurons located in the translucent band of the spinal cord slices. Of 11 neurons examined, 5 showed increased input resistance (Rin) and were depolarized in response to morphine applied in the superfusate. One neuron showed no change in Rin or potential with morphine, whereas 5 of the 11 were hyperpolarized with decreased Rin.(ABSTRACT TRUNCATED AT 400 WORDS)


2007 ◽  
Vol 97 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Hong-Mei Zhang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan

Activation of spinal muscarinic acetylcholine receptors (mAChRs) produces analgesia and inhibits dorsal horn neurons through potentiation of GABAergic/glycinergic tone and inhibition of glutamatergic input. To investigate the mAChR subtypes involved in the inhibitory effect of mAChR agonists on glutamate release, evoked excitatory postsynaptic currents (eEPSCs) were recorded in lamina II neurons using whole cell recordings in rat spinal cord slices. The nonselective mAChR agonist oxotremorine-M concentration-dependently inhibited the monosynaptic and polysynaptic EPSCs elicited by dorsal root stimulation. Interestingly, oxotromorine-M caused a greater inhibition of polysynaptic EPSCs (64.7%) than that of monosynaptic EPSCs (27.9%). In rats pretreated with intrathecal pertussis toxin, oxotremorine-M failed to decrease monosynaptic EPSCs but still partially inhibited the polysynaptic EPSCs in some neurons. This remaining effect was blocked by a relatively selective M3 antagonist 4-DAMP. Himbacine, an M2/M4 antagonist, or AFDX-116, a selective M2 antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M4 antagonist MT-3 did not alter the effect of oxotremorine-M on monosynaptic EPSCs. Himbacine also partially attenuated the effect of oxotremorine-M on polysynaptic EPSCs in some cells and this effect was abolished by 4-DAMP. Furthermore, oxotremorine-M significantly decreased spontaneous EPSCs in seven of 22 (31.8%) neurons, an effect that was blocked by 4-DAMP. This study provides new information that the M2 mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M3 and M2/M4 subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn.


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