Differences in activation of the motoneurone inhibitory receptors in a frog Rana ridibunda by GABA and glycine and their interaction

The membrane potential responses evoked by GABA and glycine bath applications were studied intracellularly in the motoneurons of the isolated frog spinal cord. The amplitude of glycine-evoked responses was 1.5-2.0 larger than that of GABA-evoked response at the same concentration. EC50 were 0.75 mM and 1.57 mM for glycine and GABA, respectively. The amplitude of responses induced by the simultaneous applications of both agonists were 79.1 +/- 2.4% (n = 19) of the sum of individual responses and 130.1 +/- 1.5% (n = 19) of individual glycine-induced responses (partial occlusion). GABA-evoked responses were decreased by 85.3 +/- 0.2% (n = 10) as a result of glycine preliminary application while preapplication of GABA reduced glycine-evoked responses only by 52.9 +/- 0.3% (n = 11). Glycine- and GABA-evoked responses were selectively suppressed by strychnine and bicuculline, respectively. These results suggest that amphibian spinal motoneurones express (less specifically than those of mammals) both glycine (predominantly) and GABAA receptors, with asymmetric cross-inhibition possibly taking place in them.     

The interaction of porphyrin precursors with GABA receptors in the isolated frog spinal cord.

Both delta aminolevulinic acid (ALA) and porphobilinogen (PBG) depressed spontaneous activity in the isolated hemisected frog spinal cord. ALA was approximately one fifth as potent as GABA in this respect and had a much slower time course. ALA hyperpolarized motoneurones and this effect was blocked by the GABA antagonist, picrotoxin, but not by the glycine antagonist, strychnine. ALA also depolarized primary afferents and this effect was similar to that of GABA although its action was somewhat reduced by strychnine. These results suggest that ALA activates the GABA receptors on motoneurones and primary afferents. The possible significance of these results to the clinical manifestations of acute attacks of porphyria is discussed.     

Three types of miniature inhibitory potentiaes in the frog spinal cord motoneurons: the possibility of GABA and glycine co-release

Miniature inhibitory postsynaptic potentials (mlPSPs) were recorded from motoneurons of the frog isolated spinal cord after blocking action potentials and ionotropic glutamate receptors (TTX 1 mcm: CNQX 25 mcm, D-AP5 50 mcm). Three types of mlPSPs were selected by their time characteristics) fast, slow and mlPSPs with two decay time constants. We classified 8.7% of mlPSPs as dual-component, 64.5% as fast mlPSPs, and 26.8% as slow mlPSPs. The GABA(A)R blocker bicuculline (20 mcm) diminished the number of the slow and dual-component events while the number of mlPSP with a fast kinetics was increased. The GlyR antagonist strychnine (1 mcm) reduced the frequency of fast mlPSPs and increased this parameter of slow mlPSPs. These data suggest existence of three different mlPSP groups distinguished by their kinetics and sensitivity to receptor antagonists: fast events mediated by glycine, slow events mediated by GABA and dual-component mlPSPs corresponding to glycine and GABA co-release.     

非洲爪蟾卵母细胞GABAB和GABAc受体介导的电流反应

实验应用双电极电压箝技术,在具有滤泡膜的非洲爪蟾(Xenopuslaevis)卵母细胞上记录到γ-氨基丁酸(γ-aminobutyricacid,GABA)-激活电流。此GABA-激活电流的特点及有关GABA受体类型的研究和分析如下(1)在35.5%(55/155)的受检细胞外加GABA可引起一慢的浓度依赖性的外向电流。(2)GABAA受体的选择性拮抗剂bicuculline(10     

The role of group II and III metabotropic glutamate receptors in modulation of miniature synaptic activity in frog spinal cord motoneurons

The results of present work demonstrate significant modulating effects mediated by group II and III mGluRs on miniature postsynaptic potentials (mPSP) of the frog spinal motoneurons. The mode of group II and III mGluRs ligands influences, i. e. the changes in the mPSPs average frequency without significant changes in their average amplitude, suggests the presynaptic mechanism of modulation by the change in transmitter release. Selective antagonists of group II and III mGluRs (EGLU and MAP4) increased the average frequency of mPSPs by 52.8 +/- 30.2% (in 4 of 6 motoneurons) and by 54.7 +/- 23.7% (in all 7 motoneurons), respectively. Application of the group III mGluRs agonist LAP4 decreased the mPSPs frequency by 21.8 +/- 5.2% in 3 of 5 motoneurons. The efficiency of the antagonist usage and comparative low efficiency of the agonist suggest that presynaptic mGluRs at motoneuronal synapses under normal condition possess some level of tonic activity. The lack of group II mGluR antagonist effect on some motoneurons appears to be explained by specific localization of the group II mGluRs in preterminal area which is distant from the transmitter release site. The hetero-receptor modulation of pharmacologically isolated inhibitory miniature activity and its glycine- and GABAergic fractions by group III mGluRs was investigated. MAP4 application has been shown to increase the glycine-mediated mlPSPs frequency more than GABA-mediated mlPSPs frequency: in average by 97.6 +/- 20.7% (n = 7) and 54.6 +/- 20.8% (n = 5), respectively. This difference may be due to the segregation of the postsynaptic glycine- and GABA-receptors. The preliminary examination of the convergence of the presynaptic mGluRs and metabotropic GABA(B) receptors influences on GABA-mediated IPSPs was undertaken. It has been shown that presynaptic GABA(B) receptors are tonically active under normal condition. Under condition of GABA(B) receptor blockage by phaclofen, the application of group III mGluR agonist L-AP4 elicited typical effect which was completely taken off by subsequent application of the group III mGluRs antagonist MAP4. This result is in accordance with the assumption that the effects mediated by GABA(B) receptors and mGluRs are independent.     

Increased γ-Aminobutyric Acid Receptor Function in the Cerebral Cortex of Myoclonic Calves with an Hereditary Deficit in Glycine/Strychnine Receptors

Inherited congenital myoclonus (ICM) of Poll Hereford cattle is a neurological disease in which there are severe alterations in spinal cord glycine-mediated neurotransmission. There is a specific and marked decrease, or defect, in glycine receptors and a significant increase in neuronal (synaptosomal) glycine uptake. Here we have examined the characteristics of the cerebral gamma-aminobutyric acid (GABA) receptor complex, and demonstrate that the malfunction of the spinal cord inhibitory system is accompanied by a change in the major inhibitory system in the cerebral cortex. In synaptic membrane preparations from ICM calves, both high-and low-affinity binding sites for the GABA agonist [3H]muscimol were found (KD = 9.3 +/- 1.5 and 227 +/- 41 nM, respectively), whereas only the high-affinity site was detectable in controls (KD = 14.0 +/- 3.1 nM). The density and affinity of benzodiazepine agonist binding sites labelled by [3H]diazepam were unchanged, but there was an increase in GABA-stimulated benzodiazepine binding. The affinity for t-[3H]butylbicyclo-o-benzoate, a ligand that binds to the GABA-activated chloride channel, was significantly increased in ICM brain membranes (KD = 148 +/- 14 nM) compared with controls (KD = 245 +/- 33 nM). Muscimol-stimulated 36Cl- uptake was 12% greater in microsacs prepared from ICM calf cerebral cortex, and the uptake was more sensitive to block by the GABA antagonist picrotoxin. The results show that the characteristics of the GABA receptor complex in ICM calf cortex differ from those in cortex from unaffected calves, a difference that is particularly apparent for the low-affinity, physiologically relevant GABA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)     

α1A-adrenergic receptor mediated pressor response to phenylephrine in anesthetized rat

To determine which subtype of α₁-adrenergic receptors plays a role in the regulation of blood pressure, with α_1A-adrenergic receptor-mediated vasoconstriction in perfused hindlimb as a control, we compared the inhibitory effects of various α₁-adrenergic receptor selective antagonists on the vasopressure responses to phenylephrine between the mean arterial pressure and hindlimb perfusion pressure in anesthetized rats. In Normotensive Wistar rats, the results showed that the inhibitory effects (dose ratios of ED₅₀, Dr) of α₁-adrenoceptor selective antagonist (prazosin, Dr 13.5 ± 3.6 vs.15.1 ± 4.3, n = 11), α_1A-adrenoceptor selective antagonist (5-methyl-urapidil, Dr 2.4 ± 0.9 vs. 3.7 ± 2.3, n = 12; RS-17053, Dr 3.2 ± 1.6 vs. 4.4 ± 3.3, n = 12) and α_1D-adrenoceptor selective antagonist (BMY7378, Dr 1.9 ± 0.9 vs. 2.2 ± 0.8, n = 8) on phenylephrine-induced increases of perfusion pressure in the autoperfused femoral beds were the same as that in the mean arterial blood pressure in normotensive Wistar rats. The inhibitory effects of antagonists (RS-17053, Dr 3.4 ± 0.6 vs. 4.3 ± 0.9, n = 5; BMY7378, Dr 1.7±0.5 vs. 1.7 ± 0.5, n = 8) in spontaneous hypertensive rats were similar with the Wistar rats. These results suggest that the mean arterial pressure induced by phenylephrine was mainly mediated by α_1A-adrenergic receptor in both the anesthetized Wistar rats and spontaneous hypertensive rats.     

The Glycine Site of the N-Methyl-D-Aspartate Receptor Channel: Differences Between the Binding of HA-966 and of 7-Chlorokynurenic Acid

The mechanisms of action of three different glycine-site antagonists of the N-methyl-D-aspartate (NMDA)-receptor channel were analyzed employing [3H]glycine direct binding assays, as well as functional glycine- and glutamate-induced uncompetitive blocker binding assays. The latter assays measure apparent channel opening. All three antagonists tested, viz., 7-chlorokynurenic acid (7-Cl-KYNA), kynurenic acid (KYNA), and 1-hydroxy-3-aminopyrrolidone-2 (HA-966), inhibited the binding of [3H]glycine to the NMDA receptor in a dose-dependent manner. These antagonists also inhibited the glycine-induced increase in accessibility of the uncompetitive blocker [3H]N-[1-(2-thienyl)cyclohexyl]-piperidine ([3H]TCP) to the channel. 7-Cl-KYNA and KYNA, but not HA-966, completely blocked the glutamate-induced binding of [3H]TCP, in a manner similar to the non-competitive manner in which the selective NMDA antagonist D-(-)-2-amino-5-phosphonovaleric acid (AP-5) inhibited glycine-induced [3H]TCP binding. The inhibitory effects of HA-966 and of AP-5 on glutamate-induced [3H]TCP binding were overcome when glutamate concentrations were increased. Of the three antagonists, 7-Cl-KYNA appears to be the most potent (Ki = 0.4-1.0 microM) and the most selective glycine antagonist. KYNA was found to act at both the glycine (Ki = 40-50 microM) and the glutamate sites. In contrast, HA-966 (Ki = 6-17 microM) appears to act either on a domain distinct from the glutamate and the glycine sites, but tightly associated with the latter, or at the glycine site, but according to a mechanism distinct from that of 7-Cl-KYNA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Action of taurine, 3-aminopropanesulfonic acid, and GABA on the hindgut and heart of the cockroach, Leucophaea maderae.

Taurine, glycine, glutamate, and gamma-aminobutyric acid (GABA) were all present in concentrations of greater than 1% of the total free amino acid content in the brain, thoracic, and abdominal ganglia of Leucophaea maderae. Hemolymph, subesophageal ganglia, and hindgut had substantial amounts of glutamate and glycine, but less than 0.3% taurine or GABA. Taurine, 3-aminopropanesulfonic acid (3-APS), cysteine-sulfinic acid (CSA), and GABA each had myotropic activity on the isolated cockroach hindgut, with 3-APS having the most consistent effect (ED50 = 0.63 mM), while taurine and CSA activities were similar to that of GABA on the hindgut. Both taurine and 3-APS had anti-arrhythmic effects on semi-isolated heart preparations of L. maderae, while GABA was inhibitory and induced arrhythmia. Bicuculline was antagonistic to the effects of GABA, taurine, and 3-APS on the hindgut, and induced arrhythmia in heart preparations; this arrhythmia was reversible by taurine, but not by GABA or 3-APS.     

Intracellular recording of the frog dorsal root single fibres' responses mediated by the GABAA and 5-HT-receptors

The effects of GABA, bicuculline and 5-HT on primary afferents in the isolated spinal cord of the frog Rana ridibunda were studied. Bath application of GABA (1 mM) reduced the primary afferent depolarisation (PAD) in IX segment of the spinal cord evoked by X dorsal root stimulation (57 +/- 8% of initial level, n = 5, p < 0.05). The action potentials (AP) recorded in dorsal root afferents was also suppressed under the GABA action (74 +/- 9%, p < 0.05). Bath application of bicuculline (50 microM) reduced the PAD (21 +/- 7%), n = 6, p < 0.05), meanwhile the AP in dorsal root afferents was resistant against the bicuculline action. Bath application of 5-HT (25 microM) depressed the PAD (34 +/- 7%, n = 7, p < 0.05) and the amplitude of the AP recorded from the single afferent fibre in dorsal column (76 +/- 6%, n = 7, p < 0.05). In contrast to GABA, 5-HT more effectively suppressed the late phase of the PAD evoked by X dorsal root stimulation and caused (76 +/- 6%, n = 7, p < 0.05) an alteration of the AP shape. All effects induced by these drugs were reversible. The mechanisms of GABA and 5-HT modulation of spinal cord afferent income are discussed.     

NMDA-mediated release of glutamate and GABA in the subthalamic nucleus is mediated by dopamine: an in vivo microdialysis study in rats

The present study investigated the effects of N-methyl-D-aspartic acid.H2O (NMDA) on the dopamine, glutamate and GABA release in the subthalamic nucleus (STN) by using in vivo microdialysis in rats. NMDA (100 micromol/L) perfused through the microdialysis probe evoked an increase in extracellular dopamine in the STN of the intact rat of about 170%. This coincided with significant increases in both extracellular glutamate (350%) and GABA (250%). The effect of NMDA perfusion on neurotransmitter release at the level of the STN was completely abolished by co-perfusion of the selective NMDA-receptor antagonist MK-801 (10 micromol/L), whereas subthalamic perfusion of MK-801 alone had no effect on extracellular neurotransmitter concentrations. Furthermore, NMDA induced increases in glutamate were abolished by both SCH23390 (8 micromol/L), a selective D1 antagonist, and remoxipride (4 micromol/L), a selective D2 antagonist. The NMDA induced increase in GABA was abolished by remoxipride but not by SCH23390. Perfusion of the STN with SCH23390 or remoxipride alone had no effect on extracellular neurotransmitter concentrations. The observed effects in intact animals depend on the nigral dopaminergic innervation, as dopamine denervation, by means of 6-hydroxydopamine lesioning of the substantia nigra, clearly abolished the effects of NMDA on neurotransmitter release at the level of the STN. Our work points to a complex interaction between dopamine, glutamate and GABA with a crucial role for dopamine at the level of the STN.     

GABA- and glycine-immunoreactive synapses in spinal cord of frog <Emphasis Type="Italic">Rana temporaria</Emphasis>

Using the method of the double immune label combined with two antibodies, i.e., monoclonal antibodies to gamma-aminobutyric acid (GABA) and polyclonal antibodies to glycine, the distribution of gamma-aminobutyric acid- and glycine-immunoreactive synapses on motoneurons and primary afferent axons was studied in the frog Rana temporaria spinal cord. An analysis of all labeled boutons on the dendrites and soma of motoneurons showed the existence of three categories of immunoreactive synapses as follows: 7% were labeled for GABA, 23% were labeled for glycine, and approximately 70% were immunoreactive to both GABA and glycine. These results confirm the predominant role of glycine in the postsynaptic inhibition of motoneuronal activity. Three similar populations of synaptic boutons were also founded on primary afferent axons, including one GABA-immunoreactive (25%) and one glycine-immunoreactive (5%); the majority of the immunoreactive synapses had the colocalization of two inhibitory transmitters. As a rule, the higher proportion of axo-axonal synapses was organized in synaptic triads. The possible simultaneous roles of glycine as a transmitter of postsynaptic inhibition and as a transmitter that mediates the process of the autoreception of glutamate in the axo-axonal synapses on the primary afferent fibers are discussed.     

SKF38393抑制大鼠DRG分离神经元GABA-激活电流

在大鼠新鲜分离ＤＲＧ神经元标本上应用全细胞膜片箝记录,观察了多巴胺Ｄ１受体的选择性激动剂ＳＫＦ３８３９３ＨＣＩ对ＧＡＢＡ－激活电流的作用。大部分受检细胞对ＧＡＢＡ敏感,１０＾－６－１０＾－３－ｍｏｌ／Ｌ ＧＡＢＡ可于引起呈剂量依赖性的明显去敏感作用的内向电流。     

NMDA and Non-NMDA Receptor-Mediated Release of [3H]GABA from Granule Cell Dendrites of Rat Olfactory Bulb

Abstract: We have studied the effect of glutamate and the glutamatergic agonists N-methyl-d -aspartate (NMDA), kainate, and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) on [³H]GABA release from the external plexiform layer of the olfactory bulb. The GABA uptake blocker nipecotic acid significantly increased the basal [³H]GABA release and the release evoked by a high K⁺ concentration, glutamate, and kainate. The glutamate uptake blocker pyrrolidine-2,4-dicarboxylate (2,4-PDC) inhibited by 50% the glutamate-induced [³H]GABA release with no change in the basal GABA release. The glutamatergic agonists NMDA, kainate, and AMPA also induced a significant [³H]GABA release. The presence of glycine and the absence of Mg²⁺ have no potentiating effect on NMDA-stimulated release; however, when the tissue was previously depolarized with a high K⁺ concentration, a significant increase in the NMDA response was observed that was potentiated by glycine and inhibited by the NMDA receptor antagonist 2-amino-5-phosphonoheptanoic acid (AP-7). The kainate and AMPA effects were antagonized by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by AP-7. The glutamate effect was also inhibited by CNQX but not by the NMDA antagonist 2-amino-5-phosphonopentanoic acid (AP-5); nevertheless, in the presence of glycine, [³H]GABA release evoked by glutamate was potentiated, and this response was significantly antagonized by AP-5. Tetrodotoxin inhibited glutamate- and kainate-stimulated [³H]GABA release but not the NMDA-stimulated release. The present results show that in the external plexiform layer of the olfactory bulb, glutamate is stimulating GABA release through a presynaptic, receptor-mediated mechanism as a mixed agonist on NMDA and non-NMDA receptors; glutamate is apparently also able to induce GABA release through heteroexchange.     

The Effect of Cyclohexyladenosine on the Penischemic Increases of Hippocampal Glutamate and Glycine in the Rabbit

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)     

γ-氨基丁酸对离体大鼠延髓头端腹外侧区神经元单位放电的抑制作用

在７３张脑片上观察了γ－氨基丁酸（ＧＡＢＡ）对１０６个延髓头端腹外侧区（ＲＶＬＭ）神经元单位放电的影响。外源性的ＧＡＢＡ（０．１￣３．０ｍｍｏｌ／Ｌ）抑制了１０６神经元中的８４个神经元的电活动,这些抑制效应呈剂量－反应关系。ＧＡＢＡ的抑制效应大部分可被ＧＡＢＡＡ受体选择性拮抗剂荷苞牡丹碱甲基碘化物（ＢＭＩ）和Ｃｌ＾－通道阻断剂印防己毒素（ＰＴＸ）所阻断,而单独灌流ＢＭＩ和ＰＴＸ对ＲＶＬＭ神经元主要     

Modulation of miniature inhibitory potentials in motoneurons of the turtle spinal cord by group II metabotropic glutamate receptors

The role of group II metabotropic glutamate receptors (mGluRs) in modulation of inhibitory synaptic activity was studied by intracellular recording of motoneuron miniature inhibitory spontaneous postsynaptic potentials (mIPSPs) in isolated lumbar segments of the turtle spinal cord in the medium containing TTX, CNQX, AP-5. The ratio of mIPSPs with fast and slow kinetics (83% vs 17%) is in accordance with the ratio shown for glycine- and GABA-mediated IPSP or IPSCs (Jones et al., 1988; Gao et al., 2001). In the majority of investigated motoneurons, the selective group II mGluRs antagonist EGLU (100-250 microM) increased the frequency of mIPSPs by 106.6 +/- 74.4% (n = 9) without affecting average amplitude, suggesting a presynaptic site of mGluRs action providing for the transmitter release reduction. The analysis of EGLU action on mIPSPs with different time courses (selection by half-width) showed that the frequency of inhancement of miniature inhibitory activity is caused by predominantly short-duration mIPSPs (ba 84.0 +/- 18.2%; n = 9), which are probably glycineergic. However, EGLU did not influence the mIPSPs frequency under condition of GABA-receptor blockade by bicuculline (20 microM). This fact suggest that group II mGluRs could modulate glycinergic transmission to the turtle spinal motoneurons on the necessary condition that GABergic system is active.     

GABA参与兔杏仁体抑制内膝体神经元电活动

本文采用多管微电极胞外记录技术观察了短纯音引起兔内膝神经元的声反应及刺激杏仁体对声反应的影响,并在此基础上观察电泳ＧＡＢＡ及其拮抗剂Ｂｉｃｕｃｕｌｌｉｎｅ的效应。实验结果表明：ＧＡＢＡ可以抑制ＭＧＢ神经元的声反应及自发放电活动,而ＧＡＢＡＡ拮抗剂Ｂｉｃｕｃｕｌｌｉｎｅ的作用则相反;电泳ＧＡＢＡ对ＭＧＢ神经元产生同刺激杏仁体一样的抑制产应,并且这种影响可被Ｂｉｃｕｃｕｌｌｉｎｅ翻转;嗅鼻沟后缘听区农     

Role of paraventricular nucleus in the cardiogenic sympathetic reflex in rats

Myocardial ischemia stimulates cardiac spinal afferents to initiate a sympathoexcitatory reflex. However, the pathways responsible for generation of increased sympathetic outflow in this reflex are not fully known. In this study, we determined the role of the paraventricular nucleus (PVN) in the cardiogenic sympathetic reflex. Renal sympathetic nerve activity (RSNA) and blood pressure were recorded in anesthetized rats during epicardial application of 10 microg/ml bradykinin. Bilateral microinjection of muscimol (0.5 nmol), a GABA(A) receptor agonist, was performed to inhibit the PVN. In 10 vehicle-injected rats, epicardial bradykinin significantly increased RSNA 178.4 +/- 48.5% from baseline, and mean arterial pressure from 76.9 +/- 2.0 to 102.3 +/- 3.3 mmHg. Microinjection of muscimol into the PVN significantly reduced the basal blood pressure and RSNA (n = 12). After muscimol injection, the bradykinin-induced increases in RSNA (111.6 +/- 35.9% from baseline) and mean arterial pressure (61.2 +/- 1.3 to 74.5 +/- 2.7 mmHg) were significantly reduced compared with control responses. The response remained attenuated even when the basal blood pressure was restored to the control. In a separate group of rats (n = 9), bilateral microinjection of the ionotropic glutamate antagonist kynurenic acid (4.82 or 48.2 nmol in 50 nl) had no significant effect on the RSNA and blood pressure responses to bradykinin compared with controls. These results suggest that the tonic PVN activity is important for the full manifestation of the cardiogenic sympathoexcitatory response. However, ionotropic glutamate receptors in the PVN are not directly involved in this reflex response.     

Mechanisms of interactions between glycine- and GABA-mediated responses in spinal cord neurons

The interactions of GABA- and glycine-mediated responses have been analyzed, the whole cell patch-clamp method being used. The response induced by co-application of glycine and GABA was a lesser one than the sum of responses induced by applying two transmitters separately. The molecular mechanisms underlying this effect have been determined. Due to applications of high concentrations of neurotransmitters it was revealed that GABA could activate glycine receptors in frog spinal motoneurons with relatively high efficiency (EC50 = 1.2 mM). The sequential application of neurotransmitters showed that even a single application of glycine could significantly boost the "run-down" of the GABA-mediated current, suggesting that there was a strong phosphorylation-dependent mechanism of GABAa-receptors inhibition. These mechanisms are likely to take place in frog spinal motoneurons when GABA and glycine are co-released from the same synaptic terminal.