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At least 19 recordsLinked to original sources
PubMed2005

Kv2.1: a voltage-gated k+ channel critical to dynamic control of neuronal excitability.

Neurons use a variety of mechanisms to dynamically control their own signaling capabilities. Regulation of voltage-dependent K+ channel localization and function has long been recognized as a major mechanism to achieve dynamic regulation of intrinsic neuronal excitability in a number of mammalian and non-mammalian neurons. Our recent evidence, together with compelling data from other laboratories, suggests that in mammalian neurons the Kv2.1 channel may play an especially prominent role in determining intrinsic neuronal excitability. Kv2.1 is widely expressed in brain and composes the majority of delayed rectifier K+ current in pyramidal neurons in cortex and hippocampus, and is also widely expressed in interneurons. Dynamic modulation of Kv2.1 localization and function by a mechanism involving activity-dependent Kv2.1 dephosphorylation dramatically impacts intrinsic excitability of neurons. Here we review previous studies of Kv2.1 localization and function in neurons, and summarize recent work regarding dynamic regulation of these characteristics. We also discuss possible roles of the Kv2.1 channel in neuronal and network excitability.

Animals↗
PubMed1984

The molecular basis of neuronal excitability.

Neurons process and transmit information in the form of electrical signals. Their electrical excitability is due to the presence of voltage-sensitive ion channels in the neuronal plasma membrane. In recent years, the voltage-sensitive sodium channel of mammalian brain has become the first of these important neuronal components to be studied at the molecular level. This article describes the distribution of sodium channels among the functional compartments of the neuron and reviews work leading to the identification, purification, and characterization of this membrane glycoprotein.

Animals↗
PubMed2006

Concentration-dependent effects of anticonvulsant enaminone methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability in vitro.

Enaminones are a novel group of compounds some of which possess anticonvulsant activity in in vivo animal models of seizures. We recently reported that some enaminones, including methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate, depress glutamate-mediated excitatory synaptic transmission and that this may contribute to their anticonvulsant activity [Kombian SB, Edafiogho IO, Ananthalakshmi KVV (2005) Anticonvulsant enaminones depress excitatory synaptic transmission in the rat brain by enhancing extracellular GABA levels. Br J Pharmacol 145:945-953]. Here we studied the effects of methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate, on the excitability of male rat (Sprague-Dawley) nucleus accumbens and hippocampal cells in vitro using whole-cell patch clamp recording techniques. At low, therapeutically relevant concentrations (0.3-10 microM), methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate reversibly suppressed action potential firing rate in a concentration-dependent manner. This action potential suppression was present when GABA(A), GABA(B) and glutamate receptors were blocked with their antagonists. Furthermore, methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate suppressed tetrodotoxin-sensitive sodium currents in these cells. At concentrations >/=100 microM, it induced inward currents and increased action potential firing frequency. The inward currents were without changes in input resistance and did not reverse polarity between -120 and -40 mV. These currents were independent of extracellular potassium, but were absent when extracellular sodium was replaced by choline and finally, were occluded by pretreatment with ouabain (200 microM). We conclude that methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate directly inhibits action potential firing at therapeutically relevant concentrations by suppressing tetrodotoxin-sensitive sodium currents, while inducing an ouabain-sensitive current at high concentrations to excite neurons. These two actions of methyl 4-(4'-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate on neuronal excitability would have therapeutic implications in future clinical use of enaminones as anticonvulsants in seizure disorders.

Action Potentials↗
PubMed2001

Decreased neuronal excitability in hippocampal neurons of mice exposed to cyclic hypoxia.

To study the physiological effects of chronic intermittent hypoxia on neuronal excitability and function in mice, we exposed animals to cyclic hypoxia for 8 h daily (12 cycles/h) for approximately 4 wk, starting at 2-3 days of age, and examined the properties of freshly dissociated hippocampal neurons in vitro. Compared with control (Con) hippocampal CA1 neurons, exposed (Cyc) neurons showed action potentials (AP) with a smaller amplitude and a longer duration and a more depolarized resting membrane potential. They also have a lower rate of spontaneous firing of AP and a higher rheobase. Furthermore, there was downregulation of the Na(+) current density in Cyc compared with Con neurons (356.09 +/- 54.03 pA/pF in Cyc neurons vs. 508.48 +/- 67.30 pA/pF in Con, P < 0.04). Na(+) channel characteristics, including activation, steady-state inactivation, and recovery from inactivation, were similar in both groups. The deactivation rate, however, was much larger in Cyc than in Con (at -100 mV, time constant for deactivation = 0.37 +/- 0.04 ms in Cyc neurons and 0.18 +/- 0.01 ms in Con neurons). We conclude that the decreased neuronal excitability in mice neurons treated with cyclic hypoxia is due, at least in part, to differences in passive properties (e.g., resting membrane potential) and in Na(+) channel expression and/or regulation. We hypothesize that this decreased excitability is an adaptive response that attempts to decrease the energy expenditure that is used for adjusting disturbances in ionic homeostasis in low-O(2) conditions.

Action Potentials↗
PubMed2003

Maturation of neuronal excitability in hippocampal neurons of mice chronically exposed to cyclic hypoxia.

To examine the effects of chronic cyclic hypoxia on neuronal excitability and function in mice, we exposed mice to cyclic hypoxia for 8 h daily (9 cycles/h) for approximately 2 wk (starting at 2-3 days of age) and examined the properties of freshly dissociated hippocampal neurons obtained from slices. Compared with control (Con) hippocampal CA1 neurons, exposed neurons (CYC) had similar resting membrane potentials (V(m)) and action potentials (AP). CYC neurons, however, had a lower rheobase than Con neurons. There was also an upregulation of the Na(+) current density (333 +/- 84 pA/pF, n = 18) in CYC compared with that of Con neurons (193 +/- 20 pA/pF, n = 27, P < 0.03). Na(+) channel characteristics were significantly altered by hypoxia. For example, the steady-state inactivation curve was significantly more positive in CYC than in Con (-60 +/- 6 mV, n = 8, for CYC and -71 +/- 3 mV, n = 14, for Con, P < 0.04). The time constant for deactivation (tau(d)) was much shorter in CYC than in Con (at -100 mV, tau(d)=0.83 +/- 0.23 ms in CYC neurons and 2.29 +/- 0.38 ms in Con neurons, P = 0.004). We conclude that the increased neuronal excitability in mice neurons treated with cyclic hypoxia is due to alterations in Na(+) channel characteristics and/or Na(+) channel expression. We hypothesize from these and previous data from our laboratory (Gu XQ and Haddad GG. J Appl Physiol 91: 1245-1250, 2001) that this increased excitability is a reflection of an enhanced central nervous system maturation when exposed to low O(2) conditions in early postnatal life.

Animals↗
PubMed2005

Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons.

The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Nav) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Nav channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Nav currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Nav channel gating, observed clinically in response to ciguatera poisoning.

Action Potentials↗
PubMed1994

Zinc modulates A-type potassium currents and neuronal excitability in snail neurons.

1. Zinc-induced actions were studied on the A-current and neuronal activity in identified and unidentified nerve cells of the snail, Helix pomatia, L., under voltage and current clamp conditions. 2. Extracellularly applied Zn2+ attenuated the peak amplitude of the A-current in a potential- and dose-dependent way (Ki = 1.8 mM at -30 mV, nH = 0.6). 3. Attenuation of the A-currents was initiated as Zn2+ shifted the potential dependence of both activation and inactivation of the currents toward more positive potential values. 4. Zinc concomitantly prolonged the time to peak and the decay time constant of the A-currents (Kd = 1.7 mM, nH = 1.4) as well. 5. Zn2+ decreased the resting membrane potential and the spike amplitude and increased the action potential duration and the input resistance of the cells in current clamp experiments. 6. A complex action of zinc increased the neuronal excitability, indicating spontaneous and synaptically evoked spike discharges. 7. Common and specific zinc binding sites are supposed on vertebrate and invertebrate A-type potassium channel proteins, where binding Zn2+ can modulate the gating properties and kinetics of the fast outward potassium currents.

Animals↗
PubMed2006

TGF-beta1-induced long-term changes in neuronal excitability in aplysia sensory neurons depend on MAPK.

Transforming growth factor beta-1 (TGF-beta1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-beta1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-beta1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-beta1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-beta1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-beta1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-beta1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.

Action Potentials↗
PubMed1999

IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system.

Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1beta and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1beta or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1beta was suppressed by the natural IL-1beta human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1beta or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.

Animals↗
PubMed2002

Oxidative and nonoxidative metabolism of excited neurons and astrocytes.

There is evidence that the metabolic responses to afferent and efferent nervous activity are dissociated at sites of neuronal excitation in brain. Whether efferent activity follows afferent activity depends on the responsiveness of postsynaptic neurons, which in turn depends on the summation of excitatory and inhibitory postsynaptic potentials. The afferent activity excites the presynaptic terminals and astrocytes, whereas the efferent activity arises from excitation of the dendrites of projection neurons. Measurements in vivo indicate that primary stimulation, elicited by simple stimuli, gives rise to limited increases of energy metabolism associated with afferent activity. Reports show that a major consequence of afferent activity, in addition to the release of excitatory neurotransmitters from presynaptic terminals and the import of glutamate by astrocytes, is the establishment of rates of blood flow commensurate with increased rates of oxidative energy metabolism associated with efferent activity projecting from the site of activation. Increased flow rates overcome the inherent diffusion limitation of oxygen delivery, while increased rates of glycolysis elevate tissue pyruvate contents, to which oxygen consumption rates are matched. In vivo, neurons in the baseline condition sustain no net import of pyruvate or lactate, and the reported changes of metabolism subserving afferent and efferent activity are additive rather than linked by significant additional transfer of pyruvate or lactate from astrocytes. The dissociation of blood flow changes from efferent activity weakens the identification of functional states by changes of blood flow alone. It raises the possibility that uncoupling of flow from oxidative metabolism occurs at sites of low efferent activity, such that dissociations of flow and glycolysis from oxygen consumption signify imbalances of afferent and efferent activity.

Adenosine Triphosphate↗
PubMed2004

Calcium signal-dependent plasticity of neuronal excitability developed postnatally.

Neuronal plasticity and its development were investigated at pyramidal neurons in the cortical slices of rats. The threshold and probability of firing spikes were measured by using whole-cell recording to assess neuronal excitability. Postsynaptic high frequency activity (HFA) at the pyramidal neurons, evoked by 20 trains (250-ms interval) of five depolarization-pulses (1 ms) at 100 Hz, persistently lowered the threshold and increased the probability of firing spikes. After long-term enhancement of neuronal excitability by HFA was stable, another HFA induced further enhancement. Infusing 1 mM 1,2-bis(2-aminophenoxy)-ethane-N, N,N',N'-tetraacetic acid or 100 microM CaMKII(281-301) into the recording neurons prevented HFA-induced long-term enhancement of neuronal excitability. The infusion of 40 microM calcineurin autoinhibitory peptide enhanced neuronal excitability, which occluded HFA effect. HFA-induced long-term enhancement of intrinsic excitability expressed at most pyramidal neurons after postnatal day (PND) 14, but not at those before PND 9. Our results show a new type of neuronal plasticity induced by physiological activity at cortical neurons, which requires calcium-dependent protein phosphorylation and develops during postnatal period. An upregulation of intrinsic excitability at cortical neurons facilitates their activity and broadens signal codes; consequently, their computational ability is upgraded.

Action Potentials↗
PubMed2002

The Drosophila melanogaster translational repressor pumilio regulates neuronal excitability.

Maintenance of proper neuronal excitability is vital to nervous system function and normal behavior. A subset of Drosophila mutants that exhibit altered behavior also exhibit defective motor neuron excitability, which can be monitored with electrophysiological methods. One such mutant is the P-element insertion mutant bemused (bem). The bem mutant exhibits female sterility, sluggishness, and increased motor neuron excitability. The bem P element is located in the large intron of the previously characterized translational repressor gene pumilio (pum). Here, by several criteria, we show that bem is a new allele of pum. First, ovary-specific expression of pum partially rescues bem female sterility. Second, pum null mutations fail to complement bem female sterility, behavioral defects, and neuronal hyperexcitability. Third, heads from bem mutant flies exhibit greatly reduced levels of Pum protein and the absence of two pum transcripts. Fourth, two previously identified pum mutants exhibit neuronal hyperexcitability. Fifth, overexpression of pum in the nervous system reduces neuronal excitability, which is the opposite phenotype to pum loss of function. Collectively, these findings describe a new role of pum in the regulation of neuronal excitability and may afford the opportunity to study the role of translational regulation in the maintenance of proper neuronal excitability.

Alleles↗
PubMed2007

Mineralocorticoid pretreatment enhances angiotensin II-induced neuronal excitation but not salt drinking in male Fischer rats.

Central administration of angiotensin (Ang) II stimulates thirst and sodium intake via the AT-1 receptor. Mineralocorticoid pretreatment enhances Ang II-induced drinking of hypertonic salt solutions (i.e. the synergy theory) in Wistar and Sprague-Dawley rats. Electrophysiological experiments using iontophoretic application of Ang II, and the AT-1 receptor specific nonpeptide antagonist losartan, have shown excitation of neurones in the preoptic/medial septum region of urethane anaesthetised male Wistar rats. Deoxycorticosterone acetate (DOCA) pretreatment further enhanced this neuronal excitation to Ang II and reduced the responses to losartan. This generated the hypothesis that DOCA-enhanced Ang II-induced neuronal excitation was necessary for the enhanced salt intake of synergy theory. We tested this hypothesis in Fischer 344 rats that are known to have a low basal salt appetite and reduced sensitivity for i.c.v. Ang II. We compared the effect of DOCA pretreatment on i.c.v. Ang II-induced water and 2% NaCl intake in behaving adult male, Fischer rats, as well as preoptic/medial septum region neuronal responses to Ang II and losartan, using a seven-barrelled micro-iontophoretic electrode sealed to a recording electrode in urethane anaesthetised, male Fischer rats. Two groups were used: one pretreated with DOCA (0.5 mg/day for 3 days) and the other comprising controls, treated with isotonic saline. Ang II applied iontophoretically increased activity in 31% of the spontaneously active neurones. Following DOCA pretreatment, the responsiveness to Ang II (when applied after aldosterone) was increased. By contrast, in the behaving animals, water and 2% NaCl intake in response to i.c.v. Ang II were not enhanced by DOCA pretreatment. These results do not support the working hypothesis but could be interpreted as evidence for the existence of two separately modulated central Ang II systems: one responding to mineralocorticoids with increased neuronal activity and the other responsible for the Ang II-induced sodium appetite in conscious rats.

Action Potentials↗
PubMed2001

Conditioning hypoxia in vivo alters neuronal excitability of hippocampal neurones of rats in vitro and in vivo.

PURPOSE: Moderate normobaric hypoxia causes long-lasting protection against damage induced by a second ischemic or traumatic insult. The changes induced by such conditioning hypoxia are not yet fully understood. The protective effect has been described in various publications but other effects seem possible. METHODS: In order to search for effects of conditioning normobaric hypoxia yet unknown, we measured O-Mg++ potentiation and classical long-term potentiation (LTP) in the CA, region of hippocampal slices seven days after the conditioning procedure. Furthermore, tests were also carried out in chronically implanted rats as to whether LTP was changed in the dentate gyrus after conditioning hypoxia. RESULTS: In slices taken from animals which received conditioning hypoxia, O-Mg++ potentiation and classical LTP of the population spike were significantly enhanced, when compared to population in two control groups. Anoxic LTP, i.e. increase in the population spike of the field potential in the dentate gyrus immediately after finishing the procedure, and a tendency to elevation of LTP seven days after conditioning were also found in chronically implanted animals which were subjected to conditioning hypoxia. CONCLUSIONS: lt. may be hypothesized that elevated Ca++ transport in the neurons during conditioning hypoxia is responsible for both long- lasting increases in plastic reactions and the protective effect.

Animals↗
PubMed2005

[Effects of milnacipran on neuronal excitability and synaptic transmission in neurons of the rat locus coeruleus].

Effects of milnacipran (MIL), a selective serotonin and noradrenaline (NA) reuptake inhibitor, on the neuronal excitability and synaptic transmission in the rat locus coeruleus (LC) were examined by intracellular and whole-cell patch-clamp recording techniques. We compared MIL and methylphenidate (MPH), a selective NA and dopamine reuptake inhibitor, as a therapeutic agent for attention deficit/hyperactivity disorder. Application of MPH (1-100 microM) and MIL (1-100 microM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response in LC neurons in a concentration-dependent manner. Spontaneous firing of LC neurons was blocked during the hyperpolarization. The MIL-induced hyperpolarization was blocked by yohimbine (1 microM), an antagonist for alpha-adrenoceptors. These results suggest that the MIL-induced hyperpolarization is mediated by NA via alpha2-adrenoceptors in LC neurons. Under the whole-cell patch-clamp condition, prolonged application of MIL produced an outward current which lasted as long as MIL existed in the ACSF. The outward current induced by NA was enhanced by MIL in LC neurons. MIL enhanced the amplitude and duration of the inhibitory postsynaptic potential, while it depressed the excitatory postsynaptic potential. The results indicated that both MIL and MPH showed almost the same effects on neuronal activity and synaptic transmission in the rat LC. These results suggest that MIL increases the concentration of NA at synaptic clefts by inhibiting the NA reuptake system in the rat LC.

Animals↗
PubMed1999

Metrifonate increases neuronal excitability in CA1 pyramidal neurons from both young and aging rabbit hippocampus.

The effects of metrifonate, a second generation cholinesterase inhibitor, were examined on CA1 pyramidal neurons from hippocampal slices of young and aging rabbits using current-clamp, intracellular recording techniques. Bath perfusion of metrifonate (10-200 microM) dose-dependently decreased both postburst afterhyperpolarization (AHP) and spike frequency adaptation (accommodation) in neurons from young and aging rabbits (AHP: p < 0.002, young; p < 0.050, aging; accommodation: p < 0.024, young; p < 0.001, aging). These reductions were mediated by muscarinic cholinergic transmission, because they were blocked by addition of atropine (1 microM) to the perfusate. The effects of chronic metrifonate treatment (12 mg/kg for 3 weeks) on CA1 neurons of aging rabbits were also examined ex vivo. Neurons from aging rabbits chronically treated with metrifonate had significantly reduced spike frequency accommodation, compared with vehicle-treated rabbits. Chronic metrifonate treatment did not result in a desensitization to metrifonate ex vivo, because bath perfusion of metrifonate (50 microM) significantly decreased the AHP and accommodation in neurons from both chronically metrifonate- and vehicle-treated aging rabbits. We propose that the facilitating effect of chronic metrifonate treatment on acquisition of hippocampus-dependent tasks such as trace eyeblink conditioning by aging subjects may be caused by this increased excitability of CA1 pyramidal neurons.

Action Potentials↗
PubMed1996

Dual action of metabotropic glutamate receptor agonists on neuronal excitability and synaptic transmission in spinal ventral horn neurons in vitro.

A dual action of selective metabotropic glutamate receptor agonists on neuronal excitability and dorsal root-evoked excitatory (DR-EPSPs) and inhibitory (DR-IPSPs) neurotransmission is described for immature rat ventral horn neurons in vitro. Trans-1-Aminocyclopentane-1,3 -dicarboxylate (trans-ACPD), its stereoisomer (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate ((1S,3R)-ACPD) and (2S,3S,4S)-alpha-(carboxycyclopropyl)-glycine (L-CCG-1) produced a concentration-related and alpha-methyl-4 -carboxyphenylglycine (MCPG)-sensitive depolarisation. An (1S,3R)-ACPD- or L-CCG-1-induced increase in intrinsic neuronal excitability was apparently independent of the depolarisation and was observed as (a) a fall in the threshold current required to elicit regenerative excitation and (b) an increased number of spikes to a fixed amplitude step depolarisation. The spike after-hyperpolarisation (AHP) duration and amplitude were reduced, suggesting an mGluR agonist action on potassium channels. Synaptic responses were depressed by the mGluR agonists. (1S,3R)-ACPD or L-CCG-1 reduced the mean +/- S.E.M. peak amplitude of a subthreshold EPSP elicited by low-intensity stimuli likely to recruit only low-threshold sensory afferents. The peak amplitude of longer-latency EPSPs elicited by higher-intensity stimuli likely to recruit high-threshold afferents in addition was attenuated. (1S,3R)-ACPD- or L-CCG-1 reduced the peak amplitude of an IPSP evoked by dorsal root stimulation. These effects on synaptic transmission were likely to be due to the combined activation of postsynaptic and presynaptic metabotropic glutamate receptors. The implications of these data for the physiological role of spinal mGluRs is discussed.

Amino Acids, Dicarboxylic↗