The globus pallidus occupies a critical position in the 'indirect' pathway of the basal ganglia and, as such, plays an important role in the modulation of movement. In recent years, the importance of the globus pallidus in the normal and malfunctioned basal ganglia is emerging. However, the function and operation of various transmitter systems in this nucleus are largely unknown. GABA is the major neurotransmitter involved in the globus pallidus. By means of electrophysiological recording, immunohistochemistry and behavioral studies, new information on the distribution and functions of the GABAergic neurotransmission in the rat globus pallidus has been generated. Morphological studies revealed the existence of GABA(A) receptor, including its benzodiazepine binding site, and GABA(B) receptor in globus pallidus. At subcellular level, GABA(A) receptors are located at the postsynaptic sites of symmetric synapses (putative GABAergic synapses). However, GABA(B) receptors are located at both pre- and postsynaptic sites of symmetric, as well as asymmetric synapses (putative excitatory synapses). Consistent with the morphological results, functional studies showed that activation of GABA(B) receptors in globus pallidus reduces the release of GABA and glutamate by activating presynaptic auto- and heteroreceptors, and hyperpolarizes pallidal neurons by activating postsynaptic receptors. In addition to GABA(B) receptor, activation of GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake change the activity of globus pallidus by prolonging the duration of GABA current. In agreement with the in vitro effect, activation of GABA(B) receptor, GABA(A) receptor benzodiazepine binding site and blockade of GABA uptake cause rotation in behaving animal. Furthermore, the GABA system in the globus pallidus is involved in the etiology of Parkinson's disease and regulation of seizures threshold. It has been demonstrated that the abnormal hypoactivity and synchronized rhythmic discharge of globus pallidus neurons associate with akinesia and resting tremor in parkinsonism. Recent electrophysiological and behavioral studies indicated that the new anti-epileptic drug, tiagabine, is functional in globus pallidus, which may present more information to understand the involvement of globus pallidus in epilepsy.
Animals ; Basal Ganglia ; metabolism ; physiology ; Epilepsy ; metabolism ; Globus Pallidus ; metabolism ; physiology ; Humans ; Parkinson Disease ; metabolism ; Presynaptic Terminals ; metabolism ; physiology ; Receptors, GABA ; physiology ; Receptors, GABA-A ; metabolism ; physiology ; Receptors, GABA-B ; metabolism ; physiology ; Synapses ; metabolism ; physiology ; gamma-Aminobutyric Acid ; metabolism

Epilepsy ; genetics ; metabolism ; Glutamic Acid ; metabolism ; Humans ; Ion Channels ; genetics ; Receptors, GABA-A ; genetics

Animals ; Anticonvulsants ; therapeutic use ; Humans ; Receptors, GABA ; genetics ; metabolism ; Seizures ; drug therapy ; genetics ; metabolism ; gamma-Aminobutyric Acid ; metabolism

Cerebellar Purkinje cells (PCs) exhibit two types of discharge activities: simple spike (SS) and complex spike (CS). Previous studies found that noradrenaline (NA) can inhibit CS and bidirectionally regulate SS, but the enhancement of NA on SS is overwhelmed by the strong inhibition of excitatory molecular layer interneurons. However, the mechanism underlying the effect of NA on SS discharge frequency is not clear. Therefore, in the present study, we examined the mechanism underlying the increasing effect of NA on SS firing of PC in mouse cerebellar cortex in vivo and in cerebellar slice by cell-attached and whole-cell recording technique and pharmacological methods. GABA_A receptor was blocked by 100 µmol/L picrotoxin in the whole process. In vivo results showed that NA significantly reduced the number of spikelets of spontaneous CS and enhanced the discharge frequency of SS, but did not affect the discharge frequency of CS. In vitro experiments showed that NA reduced the number of CS spikelets and after hyperpolarization potential (AHP) induced by electrical stimulation, and increased the discharge frequency of SS. NA also reduced the amplitude of excitatory postsynaptic current (EPSC) of parallel fiber (PF)-PC and significantly increased the paired-pulse ratio (PPR). Application of yohimbine, an antagonist of α2-adrenergic receptor (AR), completely eliminated the enhancing effect of NA on SS. The α2-AR agonist, UK14304, also increased the frequency of SS. The β-AR blocker, propranolol, did not affect the effects of NA on PC. These results suggest that in the absence of GABA_A receptors, NA could attenuate the synaptic transmission of climbing fiber (CF)-PC via activating α2-AR, inhibit CS activity and reduce AHP, thus enhancing the SS discharge frequency of PC. This result suggests that NA neurons of locus coeruleus can finely regulate PC signal output by regulating CF-PC synaptic transmission.
Action Potentials/physiology* ; Animals ; Cerebellar Cortex/metabolism* ; Cerebellum/metabolism* ; Mice ; Norepinephrine/pharmacology* ; Purkinje Cells/metabolism* ; Receptors, Adrenergic, alpha-2/metabolism* ; Receptors, GABA-A/metabolism*

OBJECTIVE: To observe the expression of GABA(A) receptor alpha1 (GABA(A)alpha1) and GABA(B) receptor 1 (GABA(B)1) in human medulla oblongata solitary nucleus and ambiguous nucleus due to tramadol-induced death. METHODS: GABA(A)alpha1 and GABA(B)1 were detected by immunohistochemical SP method in tramadol-induced death group and control group. All results were evaluated by images analysis system. RESULTS: Low expression of GABA(A)alpha1 and GABA(B)1 were detected in solitary nucleus and ambiguous nucleus in the control brain tissue. In cases of tramadol-induced death, the expression of GABA(A)alpha1 and GABA(B)1 significantly increased. CONCLUSION The mechanism of tramadol intoxication death could be caused by respiratory depression induced by over-expression of GABA(A)alpha1 and GABA(B)1 in medulla oblongata solitary nucleus and ambiguous nucleus.
Adult ; Analgesics, Opioid/poisoning* ; Autopsy ; Case-Control Studies ; Cause of Death ; Female ; Forensic Toxicology ; Humans ; Immunohistochemistry ; Male ; Medulla Oblongata/metabolism* ; Receptors, GABA-A/metabolism* ; Receptors, GABA-B/metabolism* ; Respiration Disorders/etiology* ; Solitary Nucleus/metabolism* ; Staining and Labeling ; Tramadol/poisoning*

OBJECTIVETo study the receptor mechanism of anti-convulsant effect of Caoguo Zhimu Decoction (CZD).

METHODSSD rats in traditional Chinese medicinal (TCM) group were given CZD by gastrogavage for 24 days, while those in the control group were given normal saline of the same volume. The difference of convulsant threshold was compared between the TCM group and the control group induced by pentylenetetrazole. Changes of gamma-aminobutyric acid A receptor (GABAAR-alpha1 ) and N-methyl-D-aspartate receptor-NR1 (NMDAR-NR1 ) protein expression in hippocampus were quantitatively and orientatively measured by Western blotting and immunohistochemistry method. The changes of the two receptors were compared by receptor ligand binding assay.

RESULTSThe expression of GABAAR-alpha1 subunit in the TCM group was higher, but expression of NR1 subunit protein showed no significant difference when compared with those of the control group. The binding properties of GABAA receptor in the TCM group was obviously raised, but there was no obvious change in NMDA receptor.

CONCLUSIONThe anticonvulsant effect of CZD may be achieved by raising expression of GABAA R-alpha1 subunit, and enhancing its binding with ligand.

Animals ; Anticonvulsants ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; drug effects ; metabolism ; Receptors, N-Methyl-D-Aspartate ; drug effects ; metabolism

OBJECTIVETo investigate the short-term effects of flurothyl-induced neonatal recurrent seizures on gamma-aminobutyric acid A receptor (GABAAR) alpha1 and beta2 subunit expression in the rat brain, and to study the relationship between the alterations of GABAAR subunits in the developing brain and seizure-induced brain injury.

METHODSSixty-four 7-day-old Sprague-Dawley rats were randomly divided into two groups: control and seizure. Seizures were induced by inhalant flurothyl daily for six consecutive days. The expression of GABAAR alpha1 and beta2 subunits protein in the cerebral cortex and the hippocampus were detected by Western blot and immunohistochemistry method 1 and 7 days after recurrent seizures.

RESULTSCompared to the control, the accumulated optical density (AOD) of GABAAR alpha1 subunit immunoreactivity (IR) in the parietal cortex, the CA3-CA4 regions and the dentate gyrus in seizure rats increased significantly 1 day after recurrent seizures (P<0.05). The AOD of GABAAR alpha1 subunit IR in the parietal cortex, the CA1-CA4 regions and the dentate gyrus in seizure rats increased significantly 7 days after recurrent seizures compared with the control (P<0.05). The expression of GABAAR alpha1 subunit in the hippicampus and the cerebral cortex increased significantly in seizure rats compared with that in control rats 1 and 7 days after recurrent seizures. After 7 days of recurrent seizures, the AOD of GABAAR beta2 subunit IR in the CA1-CA2 regions increased significantly in the seizure group compared with that in the control group (P<0.05), but the AOD of GABAAR beta2 subunit IR in the thalamus decreased significantly in the seizure group compared with that in the control group (P<0.05). The expression of GABAAR beta2 subunit protein in the hippocampus increased significantly in the seizure group compared with that in the control group 7 days after recurrent seizures (P<0.05).

CONCLUSIONSRecurrent neonatal seizures may result in the short-term alterations of GABAAR alpha1 and beta2 subunits expression in the cerebral cortex and the hippocampus in rats, suggesting the alterations of GABAAR subunit expression may be related to the developing brain injury following recurrent seizures.

Animals ; Animals, Newborn ; Blotting, Western ; Brain Chemistry ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA-A ; analysis ; Recurrence ; Seizures ; metabolism

AIMTo clone and analyse the coding cDNA sequence of alpha1, beta2 and gamma2 subunit of GABAA receptor in American king Pigeon.

METHODSWithdrew total RNA from the American king pigeon brain, reverse transcribing general primers to acquire a gene set cDNA. Designing specific primers of three subunit mRNA of the GABAA receptor, by RT-PCR respectively expanded the conservative gene of al subunit, beta2 subunit and gamma2 subunit of GABAA receptor, and carried on clone, plastid identification and the sequence measurese of three genes.

RESULTSThe experiment on sequence measures has succeeded that sequence analysis indicated that lengths of the conservative gene of alpha1 subunit, beta2 subunit and gamma2 subunit of GABAA receptor was respectively 899 bp, 597 bp and 563 bp, homology on reference sequence was respectively 94.99%, 94.64% and 96.28%.

CONCLUSIONHomology is high on the conservative gene of alpha1 subunit, beta2 subunit and gamma2 subunit of GABAA receptor of brain tissue of pigeon and chicken but there is a discriminating characteristic in different kinds of animals.

Animals ; Brain ; metabolism ; Cloning, Molecular ; Columbidae ; DNA, Complementary ; genetics ; RNA, Messenger ; genetics ; Receptors, GABA-A ; classification ; genetics ; Sequence Analysis, DNA

OBJECTIVETo investigate the pharmacological modulatory properties of noradrenaline in the rat spiral ganglion neuron.

METHODSNystatin perforated patch recording technique under voltage-clamp conditions was used to record the modulatory effect of noradrenaline on the current evoked by gamma-amino butyric acid (GABA) in the spiral ganglion neuron.

RESULTSThe reversal potential of the GABA response was about (- 0.78 +/- 0.05) mV (n = 8), which was almost identical to the theoretical Cl- equilibrium potential. At the holding potential of -50 mV, GABA evoked inward current (I(GABA)) over the concentration range of 0.3 to 1 micromol/L. The EC50 and Hill coefficient for GABA were (5.2 +/- 0.5) micromol/L and 1.03 (n = 26). The I(GABA) was suppressed by bicuculline, the selective GABA-A receptor antagonist, and the chloride currents evoked by GABA was inhibited by noradrenaline.

CONCLUSIONSThe result indicates that noradrenaline depressed GABA-A receptor-gated chloride currents, which may contribute to the modulatory effect of sympathetic system on auditory transmission.

Animals ; Chloride Channels ; drug effects ; GABA-A Receptor Antagonists ; pharmacology ; Neurons ; drug effects ; metabolism ; Norepinephrine ; pharmacology ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Receptors, GABA ; metabolism ; Spiral Ganglion ; drug effects

In the present study, the modulatory effect of AMPA receptors on gamma-aminobutyric acid (GABA) transporter current was investigated on enzymatically isolated horizontal cells of carp retina. The GABA transporter current elicited by 1 mmol/L GABA was decreased immediately after pre-application of AMPA (30 mumol/L or 3 mmol/L) for 50 s. Application of 10 mmol/L BAPTA in intracellular solution inhibited the suppression effect of AMPA on GABA transporter current. The suppression effect induced by co-application of 3 mmol/L AMPA and 3 mmol/L NMDA was similar to that of 3 mmol/L AMPA or 3 mmol/L NMDA alone. These results suggest that the activation of AMPA receptors inhibits GABA transporter-mediated current by affecting intracellular Ca(2+) processes in the retinal horizontal cells, which is identical with the modulatory effect of NMDA receptors on GABA transporters.
Animals ; Carps ; Egtazic Acid ; analogs & derivatives ; pharmacology ; GABA Plasma Membrane Transport Proteins ; metabolism ; Receptors, Ionotropic Glutamate ; metabolism ; Retinal Horizontal Cells ; metabolism ; gamma-Aminobutyric Acid ; pharmacology