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Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex.
Cereb Cortex. 2007 Aug; 17(8):1782-7.CC

Abstract

Fast inhibitory synaptic transmission is primarily mediated by synaptically released gamma-aminobutyric acid (GABA) acting on postsynaptic GABA(A) receptors. GABA acting on GABA(A) receptors produces not only phasic but also tonic inhibitions by persistent activation of extrasynaptic receptors. However, the mechanistic characteristics of tonic inhibition in the neocortex are not well-understood. To address this, we studied pharmacologically isolated GABA(A) receptor-mediated currents in neocortical pyramidal neurons in rat brain slices. Bath application of bicuculline blocked miniature inhibitory postsynaptic currents (mIPSCs) and produced an outward shift in baseline holding current (I(hold)). Low concentrations of SR95531, a competitive GABA(A) receptor antagonist, abolished mIPSCs but had no significant effect on I(hold). The benzodiazepine midazolam produced an inward shift in I(hold) by augmenting tonic GABA(A) receptor-mediated currents, which were significantly greater in layer V neurons than in layer II/III. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a relatively higher expressions of alpha1 and alpha5 subunit mRNA in layer V neurons. L-655708, an alpha5 subunit-specific inverse agonist, reduced tonic currents in layer V but not in layer II/III neurons, whereas zolpidem, an alpha1-subunit agonist, exerted equivalent effects in both layers. These data suggest that the alpha1 GABA(A) receptor subunit is generally involved in tonic inhibition in pyramidal neurons of the neocortex, whereas the alpha5 subunit is specifically involved in layer V neurons.

Authors+Show Affiliations

Department of Biological Information Processing, Graduate School of Electronic Science and Technology, Shizuoka University, Hamamatsu, Shizuoka 432-8011, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16997904

Citation

Yamada, Junko, et al. "Molecular Basis for the GABAA Receptor-mediated Tonic Inhibition in Rat Somatosensory Cortex." Cerebral Cortex (New York, N.Y. : 1991), vol. 17, no. 8, 2007, pp. 1782-7.
Yamada J, Furukawa T, Ueno S, et al. Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex. Cereb Cortex. 2007;17(8):1782-7.
Yamada, J., Furukawa, T., Ueno, S., Yamamoto, S., & Fukuda, A. (2007). Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex. Cerebral Cortex (New York, N.Y. : 1991), 17(8), 1782-7.
Yamada J, et al. Molecular Basis for the GABAA Receptor-mediated Tonic Inhibition in Rat Somatosensory Cortex. Cereb Cortex. 2007;17(8):1782-7. PubMed PMID: 16997904.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular basis for the GABAA receptor-mediated tonic inhibition in rat somatosensory cortex. AU - Yamada,Junko, AU - Furukawa,Tomonori, AU - Ueno,Shinya, AU - Yamamoto,Sumii, AU - Fukuda,Atsuo, Y1 - 2006/09/22/ PY - 2006/9/26/pubmed PY - 2007/9/12/medline PY - 2006/9/26/entrez SP - 1782 EP - 7 JF - Cerebral cortex (New York, N.Y. : 1991) JO - Cereb Cortex VL - 17 IS - 8 N2 - Fast inhibitory synaptic transmission is primarily mediated by synaptically released gamma-aminobutyric acid (GABA) acting on postsynaptic GABA(A) receptors. GABA acting on GABA(A) receptors produces not only phasic but also tonic inhibitions by persistent activation of extrasynaptic receptors. However, the mechanistic characteristics of tonic inhibition in the neocortex are not well-understood. To address this, we studied pharmacologically isolated GABA(A) receptor-mediated currents in neocortical pyramidal neurons in rat brain slices. Bath application of bicuculline blocked miniature inhibitory postsynaptic currents (mIPSCs) and produced an outward shift in baseline holding current (I(hold)). Low concentrations of SR95531, a competitive GABA(A) receptor antagonist, abolished mIPSCs but had no significant effect on I(hold). The benzodiazepine midazolam produced an inward shift in I(hold) by augmenting tonic GABA(A) receptor-mediated currents, which were significantly greater in layer V neurons than in layer II/III. Single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) revealed a relatively higher expressions of alpha1 and alpha5 subunit mRNA in layer V neurons. L-655708, an alpha5 subunit-specific inverse agonist, reduced tonic currents in layer V but not in layer II/III neurons, whereas zolpidem, an alpha1-subunit agonist, exerted equivalent effects in both layers. These data suggest that the alpha1 GABA(A) receptor subunit is generally involved in tonic inhibition in pyramidal neurons of the neocortex, whereas the alpha5 subunit is specifically involved in layer V neurons. SN - 1047-3211 UR - https://www.unboundmedicine.com/medline/citation/16997904/Molecular_basis_for_the_GABAA_receptor_mediated_tonic_inhibition_in_rat_somatosensory_cortex_ L2 - https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bhl087 DB - PRIME DP - Unbound Medicine ER -