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Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate
It is known that desensitization of GABA(A) receptor (GABA(A)R)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABA(A)R-mediated currents but paradoxic...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014398/ https://www.ncbi.nlm.nih.gov/pubmed/31952324 http://dx.doi.org/10.3390/ijms21020563 |
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author | Kang, Youngnam Saito, Mitsuru Toyoda, Hiroki |
author_facet | Kang, Youngnam Saito, Mitsuru Toyoda, Hiroki |
author_sort | Kang, Youngnam |
collection | PubMed |
description | It is known that desensitization of GABA(A) receptor (GABA(A)R)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABA(A)R-mediated currents but paradoxically prolongs the decay phase of inhibitory postsynaptic currents/potentials without appreciable diminution of their amplitudes. The paradoxical correlation between desensitization and resensitization of GABA(A)R-mediated currents can be more clearly seen in response to a prolonged application of GABA to allow more desensitization, instead of brief pulse used in previous studies. Indeed, hump-like GABA(A)R currents were produced after a strong desensitization at the offset of a prolonged puff application of GABA in pyramidal cells of the barrel cortex, in which calcineurin activity was enhanced by deleting phospholipase C-related catalytically inactive proteins to enhance the desensitization/resensitization of GABA(A)R-mediated currents. Hump-like GABA(A)R currents were also evoked at the offset of propofol or barbiturate applications in hippocampal or sensory neurons, but not GABA applications. Propofol and barbiturate are useful to treat benzodiazepine/alcohol withdrawal syndrome, suggesting that regulatory mechanisms of desensitization/resensitization of GABA(A)R-mediated currents are important in understanding benzodiazepine/alcohol withdrawal syndrome. In this review, we will discuss the molecular and regulatory mechanisms underlying the desensitization and resensitization of GABA(A)R-mediated currents and their functional significances. |
format | Online Article Text |
id | pubmed-7014398 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70143982020-03-09 Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate Kang, Youngnam Saito, Mitsuru Toyoda, Hiroki Int J Mol Sci Review It is known that desensitization of GABA(A) receptor (GABA(A)R)-mediated currents is paradoxically correlated with the slowdown of their deactivation, i.e., resensitization. It has been shown that an upregulation of calcineurin enhances the desensitization of GABA(A)R-mediated currents but paradoxically prolongs the decay phase of inhibitory postsynaptic currents/potentials without appreciable diminution of their amplitudes. The paradoxical correlation between desensitization and resensitization of GABA(A)R-mediated currents can be more clearly seen in response to a prolonged application of GABA to allow more desensitization, instead of brief pulse used in previous studies. Indeed, hump-like GABA(A)R currents were produced after a strong desensitization at the offset of a prolonged puff application of GABA in pyramidal cells of the barrel cortex, in which calcineurin activity was enhanced by deleting phospholipase C-related catalytically inactive proteins to enhance the desensitization/resensitization of GABA(A)R-mediated currents. Hump-like GABA(A)R currents were also evoked at the offset of propofol or barbiturate applications in hippocampal or sensory neurons, but not GABA applications. Propofol and barbiturate are useful to treat benzodiazepine/alcohol withdrawal syndrome, suggesting that regulatory mechanisms of desensitization/resensitization of GABA(A)R-mediated currents are important in understanding benzodiazepine/alcohol withdrawal syndrome. In this review, we will discuss the molecular and regulatory mechanisms underlying the desensitization and resensitization of GABA(A)R-mediated currents and their functional significances. MDPI 2020-01-15 /pmc/articles/PMC7014398/ /pubmed/31952324 http://dx.doi.org/10.3390/ijms21020563 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kang, Youngnam Saito, Mitsuru Toyoda, Hiroki Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title | Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title_full | Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title_fullStr | Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title_full_unstemmed | Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title_short | Molecular and Regulatory Mechanisms of Desensitization and Resensitization of GABA(A) Receptors with a Special Reference to Propofol/Barbiturate |
title_sort | molecular and regulatory mechanisms of desensitization and resensitization of gaba(a) receptors with a special reference to propofol/barbiturate |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014398/ https://www.ncbi.nlm.nih.gov/pubmed/31952324 http://dx.doi.org/10.3390/ijms21020563 |
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