Structure and function of cerebral GABAA and GABAB receptors

Kuriyama, Kinya; Hirouchi, Masaaki; Nakayasu, Hiroshi

doi:10.1016/0168-0102(93)90087-7

Cited by 37 publications

(15 citation statements)

References 46 publications

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“…The differences in GABA A and GABA B receptor structure (Barnard et al, 1992;Kuriyama et al, 1993;Stephenson, 1995) and signal transduction mechanisms (Alger and Nicoll, 1982;Schofield et al, 1987;Dutar and Nicoll, 1988) make it less likely that the enhancement of both responses is attributable to a single postsynaptic modification. A simpler hypothesis is that inhibitory output of GABAergic interneurons is increased after K A seizures, producing enhanced levels of synaptic GABA release that act indiscriminately on both GABA A and GABA B receptors.…”

Section: Discussionmentioning

confidence: 99%

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors

Haas¹,

Sperber

Moshé

et al. 1996

J. Neurosci.

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Seizures cause a persistent enhancement in dentate synaptic inhibition concurrent with, and possibly compensatory for, seizure-induced hippocampal hyperexcitability. To study this phenomenon, we evoked status epilepticus in rats with systemic kainic acid (K A), and 2 weeks later assessed granule cell inhibition with paired-pulse stimulation of the perforant path (PP) in vitro. Controls demonstrated three components of paired-pulse inhibition: early inhibition (10 -30 msec), intermediate facilitation (30 -120 msec), and late inhibition (120 msec to 120 sec). After seizures, inhibition in all components was enhanced significantly. The GABA A antagonist bicuculline blocked only early enhanced inhibition, demonstrating that both GABA A and GABA B postsynaptic receptors contribute to seizure-induced enhanced inhibition. In controls, the GABA B antagonist CGP 35348 increased both GABA A and GABA B responses in granule cells, suggesting that CGP 35348 acts presynaptically, blocking receptors that suppress GABA release. In contrast, slices from K A-treated rats were markedly less sensitive to CGP 35348. To test the hypothesis that GABA B receptors regulating GABA release are downregulated after seizures, we measured paired-pulse suppression of recurrent IPSPs, or disinhibition, using mossy fiber stimuli. Early disinhibition (Ͻ 200 msec) was reduced after seizures, whereas late disinhibition remained intact. CGP 35348 blocked the early component of disinhibition in controls and, to a lesser extent, reduced disinhibition in K A slices. However, paired monosynaptic IPSPs recorded intracellularly showed no difference in disinhibition between groups. Our findings indicate that seizure-induced enhancement in dentate inhibition is caused, at least in part, by reduced GABA B function in the polysynaptic recurrent inhibitory circuit, resulting in reduced disinhibition and heightened GABA release.

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Section: Discussionmentioning

confidence: 99%

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors

Haas¹,

Sperber

Moshé

et al. 1996

J. Neurosci.

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“…It is possible that GABAB receptor activation has some posttranscriptional effect on GABAA receptor function, perhaps via a second messenger system mediating phosphorylation of GABAA receptor subunits. Activation of GABAB receptors has been shown to inhibit adenylyl cyclase activity (54)(55)(56), which should lead to reduced protein kinase A (PKA) activity. Therefore, antagonism of constitutively activated GABAB receptors, as might occur in our study, should then lead to enhanced cyclic AMP levels and PKA activity.…”

Section: Discussionmentioning

confidence: 99%

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

Wan

Berton

Madamba

et al. 1996

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

130

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Despite considerable evidence that ethanol can enhance chloride flux through the y-aminobutyric acid type A (GABAA) receptor-channel complex in several central neuron types, the effect ofethanol on hippocampal GABAergic systems is still controversial. Therefore, we have reevaluated this interaction in hippocampal pyramidal neurons subjected to local monosynaptic activation combined with pharmacological isolation of the various components of excitatory and inhibitory synaptic potentials, using intracellular currentand voltage-clamp recording methods in the hippocampal slice. In accord with our previous findings, we found that ethanol had little effect on compound inhibitory postsynaptic potentials/currents (IPSP/Cs) containing both GABAA and GABAB components. However, after selective pharmacological blockade of the GABAB component of the IPSP (GABAB-IPSP/C) by low It is common knowledge that alcohol intoxication and the resulting loss of motor and cognitive control in humans have led to untold trauma and suffering. Despite the likelihood that such problems arise from the action of ethanol on the central nervous system (CNS) and several decades of alcohol research suggesting a general depressant effect of intoxicating doses of ethanol on CNS neurons, until recently little has been known about the mechanisms behind this depression. Studies over the past decade have shown that the most sensitive site for ethanol action is the synapse (1-5), and more recently it has been suggested that ethanol-evoked neuronal depression might arise from either a blunting of excitatory glutamatergic synaptic transmission (see, e.g., refs. 6-8) and/or an enhancement of inhibitory y-aminobutyric acid (GABA)ergic transmission (see refs. 4 and 9).With regard to inhibitory neurotransmission, ethanol has often been reported to enhance GABAA receptor activation, and the resulting Cl-currents or fluxes, in neurons or isolated preparations of several brain regions (4,9 (see refs. 24-26). In addition, the development of local or focal stimulation techniques (27,28), combined with these selective antagonists, now allows study of pharmacologically isolated synaptic components. Therefore, we have repeated earlier studies of ethanol effects on GABAergic monosynaptic IPSPs with two different slice preparation methods, including the one used in previous studies from our laboratory (13), but now with pharmacologically isolated IPSP components. We now report that, under these conditions, low ethanol concentrations reproducibly enhance GABAAergic IPSPs of hippocampal pyramidal neurons (HPNs), but only when GABAB receptors are blocked.MATERIALS AND METHODS Preparation. The two hippocampal slice preparations used were as described (13,29,30). In brief, male Sprague-Dawley Abbreviations: IPSP/C, inhibitory postsynaptic potential/current; IPSC, inhibitory postsynaptic current; HPN, hippocampal pyramidal neuron; GABA, y-aminobutyric acid; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; d-APV, DL-2-amino-5-phosphonovaleric acid; ACSF, artificial cer...

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“…Although GABA and glutamate are considered to be the major inhibitory and excitatory neurotransmitters, respectively, in the adult brain [7,8] including the hypo thalamus [9,10], both have been found to promote neuro peptide secretion from GnRH neurons. Glutamate (or Nmethyl-D-aspartic acid [NMDA]) stimulates GnRH re lease in vitro [11][12][13] and in vivo [14], and GABA increases GnRH release in vitro [15][16][17], However, GABA has also been reported to exert both excitatory [ 18] and inhibitory [19] effects on luteinizing hormone or GnRH release in vivo.…”

Section: Introductionmentioning

confidence: 99%

L-Type Ca2+ Channels Mediate Joint Modulation by Gamma-Amino-butyric Acid and Glutamate of [Ca2+]i and Neuropeptide Secretion in Immortalized Gonadodropin-Releasing Hormone Neurons

et al. 1995

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To examine the role of calcium signaling in the joint modulation of gonadotropin-releasing hormone (GnRH) secretion by γ-aminobutyric acid (GABA) and glutamate, cytoplasmic calcium ([Ca²⁺]_i) responses to the two transmitters were analyzed in monolayer networks of the GT1–7 line of immortalized GnRH neurons. [Ca²⁺]_i was increased by GABA and the GABA_A receptor agonist, muscimol, and these responses were inhibited by the GABAA receptor antagonist, bicuculline. In contrast, the GABA_B receptor agonist, baclofen, and the GABA_B receptor antagonist, phaclofen, had no effect on basal and GABA- and glutamate-induced Ca²⁺ levels in GT1–7 neurons. The GABA-and muscimol-induced responses consisted of a spike increase in [Ca²⁺]_i followed by a decrease to a plateau; both the increase and the subsequent decrease in [Ca²⁺]_i depended on agonist concentration. Glutamate, N-methyl-D-aspartate (NMDA), and kainate also increased [Ca²⁺]_i, but were less effective than GABA. GABA-, glutamate-, NMDA-, and kainate-induced [Ca²⁺]_i responses were almost abolished in Ca²⁺-free medium and were markedly attenuated by nifedipine. The [Ca²⁺]_i response to GABA was unaffected by prior application of glutamate, and vice versa. This additive effect of glutamate on the GABA-induced [Ca²⁺]_i response was mimicked by prior or simultaneous application of low (10 mM) KC1. The [Ca²⁺]_i response to simultaneous application of GABA and glutamate was also equal to the sum of the individual responses, whereas the GnRH secretory response was larger. However, the secretory responses to GABA and glutamate applied individually or together, were markedly attenuated by nifedipine. These results indicate that in GT1–7 neurons the combined actions of GABA and glutamate on [Ca²⁺]_i are additive of the actions of each transmitter, which are nifedipine-sensitive. However, the combined actions of the two transmitters on GnRH release are more than additive, possibly reflecting the non-linear coupling between [Ca²⁺]_i and exocytosis in neuroendocrine cells.

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Structure and function of cerebral GABAA and GABAB receptors

Cited by 37 publications

References 46 publications

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

L-Type Ca<sup>2+</sup> Channels Mediate Joint Modulation by Gamma-Amino-butyric Acid and Glutamate of [Ca<sup>2+</sup>]<sub>i</sub> and Neuropeptide Secretion in Immortalized Gonadodropin-Releasing Hormone Neurons

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Structure and function of cerebral GABAA and GABAB receptors

Cited by 37 publications

References 46 publications

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABABReceptors

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABABReceptors

Low ethanol concentrations enhance GABAergic inhibitory postsynaptic potentials in hippocampal pyramidal neurons only after block of GABAB receptors.

L-Type Ca<sup>2+</sup> Channels Mediate Joint Modulation by Gamma-Amino-butyric Acid and Glutamate of [Ca<sup>2+</sup>]<sub>i</sub> and Neuropeptide Secretion in Immortalized Gonadodropin-Releasing Hormone Neurons

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Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors

Kainic Acid-Induced Seizures Enhance Dentate Gyrus Inhibition by Downregulation of GABA_BReceptors