Different Types Of GABA Receptors Research Articles

Formation of GABAergic Neural Networks in the Bötzinger Complex in Rats in the Early Postnatal Period in Normal Conditions and with Prenatal Deficiency of Endogenous Serotonin

The dynamics of the distribution of GABAergic neurons and neurons expressing different types of GABA receptors (GABA-Aα1 and GABA-B1) in the Botzinger complex during the early postnatal period (the period of functional maturation of the receptor system in mammals) were studied in normal conditions and after prenatal reductions in serotonin content in Wistar rats. Brains from rat pups of two groups were studied on days 5, 9, and 20 after birth: controls (n = 9), born to intact females, and experimental (n = 13), born to mothers treated with parachlorophenylalanine during pregnancy to decrease endogenous serotonin content. GABA-synthesizing neurons and neurons expressing GABA-Aα1 and GABA-B1 receptors were detected immunocytochemically. Maturation of the inhibitory GABAergic network in the Botzinger complex occurred during the early postnatal period (by day 9). GABA production occurred simultaneously with GABA-Aα1 and GABA-B1 expression, though their maturation differed. GABA-Aα1 receptors formed earlier (by day 9) and coincided in time with GABA expression. Maturation of GABA-B1 receptors occurred later – only by week 3. Prenatal serotonin deficit led to a delay in the expression of GABA and GABA-Aα1 receptors in neurons of this nucleus and produced impairment to the formation of a network of terminals and synapses containing GABA and GABA-Aα1 and GABA-B1 receptors.

FORMATION OF GABA-ERGIC NEURAL NETWORK IN BÖTZINGER COMPLEX IN RATS DURING EARLY POSTNATAL PERIOD IN NORM AND IN PRENATAL DEFICIENCY OF ENDOGENOUS SEROTONIN

The dynamics of the distribution of GABAergic neurons and neurons expressing different types of GABA receptors (GABAAα1 and GABAB1) was studied in Bötzingercomplex (BötC) in the early postnatal period (the period of functional maturation of the respiratory system in mammals) in norm and prenatal reduction of serotonin content in Wistar rats. The brain was studied on postnatal Days 5, 9 and 20 in two groups of rat pups: control (n=9), born by intact females, and experimental (n=13), born from mothers that received parachlorophenylalanine, causing the depression of endogenous serotonin level. Imunocytochemical methods were used to detect the neurons producing GABA and expressing GABA and GABA Aα1B1 receptors. It was shown that the maturation of the inhibitory GABAergic network in BötC occurred in the early postnatal period (by Day 9). Simultaneously with GABA, the expression of GABA and GABA Aα1B1 receptors took place, however their maturation has the distinctive features. The formation of GABAAα1 receptors occurred earlier (by Day 9) and coincided in time with the expression of GABA. The maturation of GABAB1 receptors happened later - only by the third week. Prenatal serotonin deficiency caused a delay in the expression of GABA and GABAAα1 receptors by the neurons of BötC, as well as the disruption of the formation of a network of terminals and synapses containing GABA, GABAAα1 and GABAB1 receptors.

Localisation of the GABA(C) receptors at the axon terminal of the rod bipolar cells of the mouse retina.

In the vertebrate retina, the rod bipolar cells make reciprocal synapses with amacrine cells at the axon terminal. Amacrine cells may perform a fine control of the transmitter release from rod bipolar cells by means of GABAergic synapses acting on different types of GABA receptors. To clarify this possibility GABA-induced currents were recorded by the patch-clamp whole cell method in rod bipolar cells enzymatically dissociated from the mouse retina. All cells tested showed a desensitising chloride-sensitive GABA-induced current. When GABA 30 microM was applied in presence of 100 microM biccuculine, a blocker of the GABA(A) receptors, a slow-desensitising component of the current still remains. This current was blocked when GABA 30 microM was applied in presence of 100 microM 3-aminopropylphosphonic acid, an antagonist of the GABA(C) receptors. The current mediated by GABA(C) receptors showed an EC50 of less that 5 microM; the ionic current through the GABA(A) receptor showed an EC50 of ca. 30 microM. Two pieces of evidence demonstrated that the GABA(C)-mediated current was localised at the axon terminal of rod bipolar cells: (1) cells lacking the axon terminal only showed the biccuculine-sensitive GABA-induced current; and (2) after mechanical section of the axon terminal, bipolar cells lost the slow-desensitising component of the GABA-induced current. We conclude that the rod bipolar cells express two types of ionotropic GABA receptors, and that the high sensitive GABA(C) receptors are mainly localised at the level of the axon terminal and therefore may contribute to the modulation of the transmitter release from the rod bipolar cell.

Three GABA Receptor-Mediated Postsynaptic Potentials in Interneurons in the Rat Lateral Geniculate Nucleus

Inhibition is crucial for the thalamus to relay sensory information from the periphery to the cortex and to participate in thalamocortical oscillations. However, the properties of inhibitory synaptic events in interneurons are poorly defined because in part of the technical difficulty of obtaining stable recording from these small cells. With the whole-cell recording technique, we obtained stable recordings from local interneurons in the lateral geniculate nucleus and studied their inhibitory synaptic properties. We found that interneurons expressed three different types of GABA receptors: bicuculline-sensitive GABA(A) receptors, bicuculline-insensitive GABA(A) receptors, and GABA(B) receptors. The reversal potentials of GABA responses were estimated by polarizing the membrane potential. The GABA(A) receptor-mediated responses had a reversal potential of approximately -82 mV, consistent with mediation via Cl(-) channels. The reversal potential for the GABA(B) response was -97 mV, consistent with it being a K(+) conductance. The roles of these GABA receptors in postsynaptic responses were also examined in interneurons. Optic tract stimulation evoked a disynaptic IPSP that was mediated by all three types of GABA receptors and depended on activation of geniculate interneurons. Stimulation of the thalamic reticular nucleus evoked an IPSP, which appeared to be mediated exclusively by bicuculline-sensitive GABA(A) receptors and depended on the activation of reticular cells. The results indicate that geniculate interneurons form a complex neuronal circuitry with thalamocortical and reticular cells via feed-forward and feedback circuits, suggesting that they play a more important role in thalamic function than thought previously.

GABAA and GABAC receptors on mammalian rod bipolar cells.

Rod bipolar (RB) cells of mammalian retinae receive synapses from different gamma-aminobutyric acid (GABAergic) amacrine cells in the inner plexiform layer (IPL). We addressed the question whether RB cells of the rabbit and of the rat retina express different types of GABA receptors at these synapses. RB cells were immunolabeled in vertical sections of rat retinae with an antibody against protein kinase C (PKC). The sections were double-labeled for the alpha 1, alpha 2, alpha 3, or gamma 2 subunits of the GABAA receptor. Punctate immunofluorescence, which represents synaptic localization, was found for all four subunits. Many of the alpha 1-, alpha 3-, or gamma 2-immunoreactive puncta coincided with the axon terminals of the PKC-immunolabeled RB cells. Sections and wholemounts of rabbit retinae were also double labeled for PKC and the rho subunits of the GABAC receptor. Rabbit RB cells were decorated by many rho-immunoreactive puncta, which were shown by electron microscopy to represent synaptic localization. Previous work from our laboratory has shown that the alpha 1, alpha 2, alpha 3, and rho subunits are not found within the same synapse but are expressed at different synaptic sites. Taken together, these results suggest that RB cells of mammalian retinae express at least three different types of GABA receptors at synaptic sites in the IPL: GABAC receptors, GABAA receptors containing the alpha 1 subunit, and GABAA receptors containing the alpha 3 subunit.

Patch-clamp recordings of spiking and nonspiking interneurons from rabbit olfactory bulb slices: GABA- and other transmitter receptors.

Transmitter receptor ion channels from previously identified rabbit olfactory bulb neurons were studied by using a thin slice preparation in combination with patch-clamp measurements. PG cells, which closely resembled previously described periglomerular interneurons in their morphology, responded to microapplication of GABA, acetylcholine, norepinephrine and glycine with the activation of distinct ionic currents. JG cells, which belong either to the class of short axon cells or external tufted cells, never showed GABA responses. In mitral cells ionic currents activated by GABA, acetylcholine, norepinephrine and glutamate could be elicited. Further measurements of GABA-activated currents of PG cells were made and indicated that these cells expressed two different types of GABA receptors: one which showed fast desensitization with a decay time constant of about 5 s, and one which slowly desensitized with a decay time constant of about 20-30 s. Both types were completely inhibited by bicuculline methiodide (50 microM). GABA receptors were not blocked by Zn2+ (0.1 mM). From the dose-response relationship of the peak GABA-activated currents, an apparent dissociation constant of 50 microM was derived. From single channel measurements in excised outside-out patches, a single channel conductance of GABA-activated Cl- currents of 24 pS was obtained during continuous application of the agonist. Single channel events had a mean open time of 1.9 ms.

Regulation of3H-dopamine release by presynaptic GABA and glutamate heteroreceptors in rat brain nucleus accumbens synaptosomes

The aim of this investigation was a neurochemical study of the effect of agonists of different types of GABA receptors - muscimol (type A receptor), baclofen (type B receptor), delta-aminolevulinic acid (DALA; GABA autoreceptor), and also of GABA itself - on tritium-labelled dopamine release, stimulated by potassium cations, from synaptosomes of the nuclei accumbenes of the rat brain.

A new class of GABA agonist

COMPOUNDS which mimic the activity of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) on postsynaptic receptors are of particular pharmacological interest as possible therapeutic agents in human neurological disorders and as molecular probes with which to study different types of GABA receptors. The GABA molecule has considerable flexibility with free rotation around all three carbon–carbon bonds as indicated in Fig. 1. This conformational mobility is reduced in GABA analogues such as trans-4-aminocrotonic acid1 and muscimol2, which are potent GABA agonists at bicuculline-sensitive receptors on spinal neurones of the cat. The conformational mobility of such compounds can be reduced still further by incorporating the amino function in a ring structure. This has led to a new class of GABA agonist described here, based on l,2,3,6-tetrahydropyridine-4-carboxylic acid (isoguvacine) and the related bicyclic isoxazole 4,5,6,7-tetra-hydroisoxazolo[5,4-c]pyridin-3-ol (THIP) (Fig. 1). Isoguvacine represents a semi-rigid analogue of trans-4-aminocrotonic acid in a folded conformation. THIP, a folded analogue of muscimol, is even more rigid as the ‘masked’ carboxyl group (the 3-isoxazolo moiety) is fixed in the general plane of the molecule. The action of these compounds as GABA agonists provides indirect evidence that GABA interacts with bicuculline-sensitive postsynaptic receptors in the cat spinal cord in a partially extended and almost planar conformation.