Direct modulation of GABAA receptor by intracellular ATP in dissociated nucleus tractus solitarii neurones of rat.

Shirasaki, Tetsuya; Aibara, Keiji; Akaike, Norio

doi:10.1113/jphysiol.1992.sp019101

Cited by 71 publications

(49 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since the GABAA response recorded by the use of conventional whole-cell mode of patch-clamp technique decreases time-dependently, 5 mM MgATP was added to the internal solution to prevent the sensitivity-loss for the affinity of GABAA receptor (run-down) (Chen et al, 1990;Shirasaki et al, 1992). When this was done, the GABA responses were maintained for more than 1 h and increased in a sigmoidal fashion with increase in the concentration of GABA.…”

Section: Resultsmentioning

confidence: 99%

Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones

Yakushiji¹,

Shirasaki

Munakata

et al. 1993

British J Pharmacology

View full text Add to dashboard Cite

4 In concentration-response relationships of BZR partial agonists, the threshold concentrations, KD values and maximal augmentation ratio of the GABA response were similar in all CTX, CPJ and SVH neurones. Also, in all preparations, the threshold concentration and KD values of diazepam action were 10 fold less than those induced by partial agonists. 5 All BZR agonists shifted the concentration-response relationship for GABA to the left without changing the maximum current amplitude, indicating that activation of both BZ1 and BZ2 increase the affinity of the GABAA receptor for GABA. 6 The results are important in clarifying the mechanism of anxiety and might explain the anxioselectivity of BZR partial agonists.

show abstract

Section: Resultsmentioning

confidence: 99%

Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones

Yakushiji¹,

Shirasaki

Munakata

et al. 1993

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…Suppression of the GABA response involved a dephosphorylation process Previous results suggested that intracellular Ca2+ suppresses the GABA response in the hippocampal cell by activating a phosphatase (Chen et al 1990; see, however, Shirasaki, Aibara & Akaike, 1992). We examined the possible involvement of dephosphorylation in the NMDAinduced suppression of the GABA response.…”

Section: Resultsmentioning

confidence: 99%

Suppression of GABAA receptor responses by NMDA application in hippocampal neurones acutely isolated from the adult guinea‐pig.

Chen

Wong

1995

The Journal of Physiology

134

View full text Add to dashboard Cite

1. In acutely isolated hippocampal cells, NMDA and glutamate application suppressed GABAA receptor-mediated responses. We studied the cellular events underlying the interaction between the two classes of receptors by using a whole-cell voltage-clamp approach. 2. Following an NMDA application, an outward current mediated by GABAA receptor activation (GABA response) was suppressed for up to 12 s. The suppression of the GABA response was reduced when Ca2+ in the extracellular solution was replaced by Ba2+ or when intracellular BAPTA (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)was increased from 1 to 10 mM. 3. Replacing ATP in the intracellular solution by adenosine-5'-0-3-thiotriphosphate reduced the suppressive effect of NMDA application on the GABA response. Okadaic acid, a phosphatase inhibitor, also prevented the NMDA-induced suppression of the GABA response. In addition, when the intracellular perfusing solution contained the calcineurin autoinhibitory fragment (50 /1M), suppression of the GABA response by the NMDA current was also reduced.

show abstract

“…9 To determine if run-down of GABA-evoked currents contributed to the differences in EC 50 between NT and HT rats, GABA was applied (1 mmol/L, 2-second duration) at the onset of a recording and every 5 minutes for 25 minutes. The peak current density after 25 minutes of recording was 94Ϯ11% of the value obtained at the onset of the recording in NT rats (nϭ8) and 95Ϯ3% in HT rats (nϭ3) (PϾ0.05).…”

Section: Time-dependent Changes In Gaba Receptor-evoked Responsesmentioning

confidence: 99%

Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

2004

View full text Add to dashboard Cite

Abstract-The inhibitory amino acid GABA is a potent modulator of the spontaneous discharge and the responses to afferent inputs of neurons in the nucleus of the solitary tract (NTS). To determine if responses to activation of GABA A receptors are altered in hypertension, GABA A receptor-evoked whole cell currents were measured in enzymatically dispersed NTS neurons from 33 normotensive (NT, 109Ϯ4 mm Hg, nϭ7) and 24 hypertensive (HT, 167Ϯ5 mm Hg, nϭ24) rats. GABA A receptor-evoked currents reversed at the calculated equilibrium potential for chloride and were blocked by bicuculline (nϭ6). Membrane capacitance was the same in neurons from NT (7.5Ϯ0.6 pF, nϭ62) and HT (6.8Ϯ0.6 pF, nϭ51) rats. The EC 50 for peak GABA-evoked currents cells was significantly greater in neurons from HT (21.0Ϯ2.6 mol/L, nϭ16) compared with NT rats (13.0Ϯ1.8 mol/L, nϭ14, Pϭ0.01). The EC 50 of neurons exhibiting DiA labeling of presumptive aortic nerve terminals was no different than that observed in the nonlabeled cells (19.0Ϯ4.9 mol/L, nϭ4). The time constant for desensitization of GABA A -evoked currents was the same in neurons from HT (4.5Ϯ0.3 seconds, nϭ17) and NT rats (3.8Ϯ0.3 seconds, nϭ17, PϾ0.05). Repetitive pulse application of GABA revealed a more rapid decline in the evoked current in neurons from HT compared with NT rats. The amplitude of the 5th pulse of GABA (5-second duration, 2-second interval) was 21Ϯ2% the amplitude of the 1st pulse in NT rats (nϭ10) and 14Ϯ2% in HT rats (nϭ11, PϽ0.05). These alterations in GABA A -receptor evoked currents could render the neurons less sensitive to GABA A receptor inhibition and influence afferent integration by NTS neurons in HT. [2][3][4] Within the NTS, activation of GABA A receptors inhibits virtually all neurons tested and results in an increase in arterial pressure, heart rate, and sympathetic outflow, effects consistent with inhibitory modulation of arterial baroreceptor reflexes. 1 The function of GABA A receptors has been shown to be modulated by a variety of factors. Receptor number, subunit composition, and phosphorylation state are but a few of the ways that GABA receptor function can be altered after chronic exposure to alcohol, barbiturates, benzodiazepines, and GABA itself. [2][3][4] Alterations in the responses of NTS neurons to GABA A receptor activation could result in alterations in the integration of afferent inputs, reflex function, and resting cardiovascular parameters. The goal of the current study was to determine if the responses of isolated NTS neurons to activation of GABA A receptors are altered in hypertension. Methods GeneralSuccessful experiments were performed on adult (1 to 3 months), male Sprague-Dawley rats (375 to 500 g, Charles River Laboratories or Harlan Sprague-Dawley Inc). Rats were housed 2 per cage in a fully accredited (Association for Assessment and Accreditation of Laboratory Animal Care and the United States Department of Agriculture) laboratory animal room with free access to food and water. All rats were given at least 1 week to acclimat...

show abstract

Direct modulation of GABAA receptor by intracellular ATP in dissociated nucleus tractus solitarii neurones of rat.

Cited by 71 publications

References 43 publications

Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones

Differential properties of type I and type II benzodiazepine receptors in mammalian CNS neurones

Suppression of GABAA receptor responses by NMDA application in hippocampal neurones acutely isolated from the adult guinea‐pig.

Responses to GABAA receptor activation are altered in NTS neurons isolated from chronic hypoxic rats

Contact Info

Product

Resources

About