Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons

Murase, Kazuyuki; Ryu, Pan Dong; Randić, Mirjana

doi:10.1016/0304-3940(89)90485-0

Cited by 418 publications

(187 citation statements)

References 18 publications

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“…Isolation of dorsal horn neurons was as described (30). The dorsal third of a spinal cord slice was treated with 0.5 mg͞ml pronase for 15 min (Calbiochem) and then 0.5 mg͞ml protease-type X for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Genzen

McGehee

2003

Proc. Natl. Acad. Sci. U.S.A.

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Spinal administration of nicotinic agonists can produce both hyperalgesic and analgesic effects in vivo. The cellular mechanisms underlying these behavioral phenomena are not understood. As a possible explanation for nicotinic hyperalgesia, we tested whether nicotinic acetylcholine receptors (nAChRs) could enhance excitatory transmission onto spinal cord dorsal horn neurons. Whole-cell patch-clamp recordings were performed in neonatal rat spinal cord slices. Activation of nAChRs enhanced glutamatergic synaptic transmission in 59% of dorsal horn neurons tested, and this effect was blocked by methyllycaconitine (10 nM), suggesting a key role for ␣7 nAChRs. Inhibition of acetylcholinesterase with methamidophos also enhanced transmission, demonstrating a similar effect of endogenous acetylcholine. nAChR activation also enhanced transmission by dorsal root entry zone stimulation, suggesting that ␣7 nAChRs on the central terminals of DRG afferents mediate this effect. Paired pre-and postsynaptic stimulation induced long-term potentiation of excitatory inputs to some of the dorsal horn neurons. Long-term potentiation induction was much more prevalent when nicotine was applied during stimulation. This effect also depended on both ␣7 nAChRs and N-methyl-D-aspartate glutamate receptors. Our findings demonstrate that ␣7 nAChRs can contribute to both short-and long-term enhancement of glutamatergic synaptic transmission in the spinal cord dorsal horn and provide a possible mechanism for nicotinic hyperalgesia.E ffective pain management is a major challenge for modern healthcare. Most pain medications fall under two classes of compounds, opioids and nonsteroidal antiinflammatory drugs. Recently, structural analogs of nicotine have also demonstrated strong analgesic potency (1, 2). Although these agents may provide alternate pain therapies, a number of issues remain to be resolved, such as addictive profiles and side effects, including paradoxical hyperalgesia. Considerable research has focused on the analgesic effects of nicotine and its analogs (2-7), yet the mechanisms underlying nicotinic hyperalgesia are not well understood.Hyperalgesia and͞or irritation have been observed after central injections of nicotinic agonists (8-10), systemic injections of subanalgesic doses (11), and intrathecal applications (12,13). This intrathecal effect is associated with significant increases in excitatory transmitter release (14), and both nicotinic and glutamate receptor antagonists can decrease this hyperalgesia (15, 16). Although dorsal horn neurons are excited by nicotine (17), it is not known which subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed by dorsal horn neurons or on presynaptic afferent terminals. For example, nicotinic enhancement of synaptic activity has been noted in the spinal cord dorsal horn (SCDH) in mice that lack the ␣4 nAChR subunit, but the nAChR subtype(s) that mediate this effect is unknown (5).Neuronal nAChRs are pentameric ligand-gated ion channels, and molecular cloning has identified nin...

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Section: Methodsmentioning

confidence: 99%

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Genzen

McGehee

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…CA1 pyramidal neurons were viewed with an upright microscope (Axioscope, Zeiss, Germany) equipped with Nomarski optics. Drugs were added to the ACSF and delivered locally with a Y-tube device [42]. Stock solutions of bicuculine metabromide (BMR; to confirm GABA postsynaptic currents (IPSCs) via inhibition of GABA receptors) and tetrodotoxin (TTX; to observe miniature (m)IPSCs) were dissolved in water.…”

Section: Whole Cell Recordings Of Ca1 Pyramidal Neuronsmentioning

confidence: 99%

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Toscano

Ueda

Tomita

et al. 2008

Brain Research Bulletin

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Excitotoxicity involves over activation of brain excitatory glutamate receptors and has been implicated in neurological, neurodegenerative and neuropsychiatric diseases. Metabolism of arachidonic acid (AA) through the phospholipase A 2 (PLA 2 )/ prostaglandin-endoperoxide synthase (PTGS) pathway is increased after excitotoxic stimulation. However, the individual roles of the PTGS isoforms in this process are not well established. We assessed the role of the PTGS isoforms in the process of excitotoxicity by exposing mice deficient in either PTGS-1 (PTGS-1 -/-) or PTGS-2 (PTGS-2 -/-) to the rototypic excitotoxin, kainic acid (KA). Seizure intensity and neuronal damage were significantly elevated in KA-exposed PTGS-2 -/-, but not in PTGS-1 -/-, mice. The increased susceptibility was not associated with an alteration in KA receptor binding activity or mediated through the CB1 endocannabinoid receptor. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was decreased in the CA1 pyramidal neurons of PTGS-2 -/-mice, suggesting an alteration of GABAergic function. In wild-type mice, six weeks treatment with the PTGS-2 selective inhibitor celecoxib recapitulated the increased susceptibility to KA-induced excitotoxicity observed in PTGS-2 -/-mice, further supporting the role of PTGS-2 in the excitotoxic process. The increased susceptibility to KA was also associated with decreased brain levels of PGE 2 , a biomarker of PTGS-2 activity. Our results suggest that PTGS-2 activity and its specific products may modulate neuronal excitability by affecting GABAergic neurotransmission. Further, inhibition of PTGS-2 but not PTGS-1, may increase the susceptibility to seizures.

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“…NMDA (0.3-300 pM) was applied directly by a gravity-fed Y-tubing deliveiy system (Murase et al, 1989) placed within 100 pm of the recorded cell. Drug application had fast onset (<10 ms) and achieved a completely local perfusion of the recorded cell.…”

Section: Drug Applicationmentioning

confidence: 99%

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93

Corsi¹,

Li²,

Krueger³

et al. 1998

Journal of Neurochemistry

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Abstract:Recordings of NMDA-activated currents from cerebellar granule neurons in culture revealed a developmental increase in current density accompanied by a slight decrease of the half-maximal effective concentration. At the same time, a decrease of NMDA receptors comprising NR2B subunits was demonstrated by the reduction in the antagonism of NMDA currents by ifenprodil. Ifenprodil antagonism increased after treatment for 24 h with KN93-and KN62-selective inhibitors of the Ca2~/calmodulin-dependentprotein kinases (CaM kinases), indicating a selective increase of receptor containing NR2B subunit. This increase was observed at all ages tested: 4 days in vitro (DIV4), DIV6, and DIV13. Western blot analysis with specific NMDA receptor antibodies performed at DIV6 confirmed the electrophysiological data. At this age, the negative control KN92 was ineffective. The increasing ifenprodil antagonism after KN93 treatment was proportionally greater in cells at DIV13 than at DIV4. Treatment with NMDA (100~tM) of cerebellar cultures for 24 h produced a decrease in the NMDA-induced current density by almost 50% at all ages tested. Ifenprodil antagonism, however, was unchanged. We propose that the expression of NR2B subunits in cerebellar granule cells is selectively stimulated by the inhibition of CaM kinases.

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Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons

Cited by 418 publications

References 18 publications

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93

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Excitatory and inhibitory amino acids and peptide-induced responses in acutely isolated rat spinal dorsal horn neurons

Cited by 418 publications

References 18 publications

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Short- and long-term enhancement of excitatory transmission in the spinal cord dorsal horn by nicotinic acetylcholine receptors

Altered GABAergic neurotransmission is associated with increased kainate-induced seizure in prostaglandin-endoperoxide synthase-2 deficient mice

Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca2+/Calmodulin Kinase Inhibitor KN93

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Up‐Regulation of NR2B Subunit of NMDA Receptors in Cerebellar Granule Neurons by Ca²⁺/Calmodulin Kinase Inhibitor KN93