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Neurosteroid modulation of benzodiazepine-sensitive GABAA tonic inhibition in supraoptic magnocellular neurons.
. 2011 Jun; 300(6):R1578-87.

Abstract

Interactions between neurosteroids and GABA receptors have attracted particular attention in the supraoptic nucleus (SON). Although GABA(A) receptors (GABA(A)R) mediate a sustained tonic inhibitory current (I(tonic)), as well as conventional phasic inhibitory postsynaptic currents (IPSCs, I(phasic)) in the SON, whether the steroid modulation on I(tonic) is present in SON magnocelluar neurosecretory cells (MNCs) is unknown. Here, we addressed this question and gained insights into the potential molecular configuration of GABA(A) receptors mediating I(tonic) and conferring its neurosteroids sensitivity in SON MNCs. 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (1 μM), a relatively selective extrasynaptic GABA(A)R agonist, facilitated I(tonic) without affecting the main characteristics of IPSCs, while DS-2, a relatively selective modulator of GABA(A)R δ-subunits, caused minimal changes in I(tonic) of SON MNCs. l-655,708, a relatively selective GABA(A)R α(5)-subunit inverse agonist, blocked ∼35% of the total I(tonic) both under basal and elevated ambient GABA concentration (3 μM). Facilitation of I(tonic) by benzodiazepines further supported the role of GABA(A)R γ(2)-subunit in I(tonic) of SON MNCs. Quantitative RT-PCR analysis showed much lesser expression of GABA(A)R δ-subunit than the α(5) or γ(2)-subunit in the SON. Allopregnanolone and 3α,5α-tetrahydrodeoxycorticosterone increased both I(tonic) and I(phasic) in SON MNCs, respectively, although more than 90% of the current increase was mediated by I(tonic) during the neurosteroid facilitation. Finally, l-655,708 attenuated the neurosteroid facilitation of I(tonic) but not of I(phasic). Altogether, our results suggest that I(tonic), mediated mainly by benzodiazepine-sensitive GABA(A)Rs containing α(5)-, β-, and γ(2)-, and to a lesser extent, δ-subunits, is a potential target of neurosteroid modulation in SON neurons.

Authors+Show Affiliations

Department of Physiology, School of Medicine, Chungnam National University, Daejeon, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

21451144

Citation

Jo, Ji Yoon, et al. "Neurosteroid Modulation of Benzodiazepine-sensitive GABAA Tonic Inhibition in Supraoptic Magnocellular Neurons." American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, vol. 300, no. 6, 2011, pp. R1578-87.
Jo JY, Jeong JA, Pandit S, et al. Neurosteroid modulation of benzodiazepine-sensitive GABAA tonic inhibition in supraoptic magnocellular neurons. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1578-87.
Jo, J. Y., Jeong, J. A., Pandit, S., Stern, J. E., Lee, S. K., Ryu, P. D., Lee, S. Y., Han, S. K., Cho, C. H., Kim, H. W., Jeon, B. H., & Park, J. B. (2011). Neurosteroid modulation of benzodiazepine-sensitive GABAA tonic inhibition in supraoptic magnocellular neurons. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 300(6), R1578-87. https://doi.org/10.1152/ajpregu.00627.2010
Jo JY, et al. Neurosteroid Modulation of Benzodiazepine-sensitive GABAA Tonic Inhibition in Supraoptic Magnocellular Neurons. Am J Physiol Regul Integr Comp Physiol. 2011;300(6):R1578-87. PubMed PMID: 21451144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neurosteroid modulation of benzodiazepine-sensitive GABAA tonic inhibition in supraoptic magnocellular neurons. AU - Jo,Ji Yoon, AU - Jeong,Ji Ae, AU - Pandit,Sudip, AU - Stern,Javier E, AU - Lee,Seul Ki, AU - Ryu,Pan Dong, AU - Lee,So Yeong, AU - Han,Seong Kyu, AU - Cho,Chung-Hyun, AU - Kim,Hyun Woo, AU - Jeon,Byeong Hwa, AU - Park,Jin Bong, Y1 - 2011/03/30/ PY - 2011/4/1/entrez PY - 2011/4/1/pubmed PY - 2011/9/17/medline SP - R1578 EP - 87 JF - American journal of physiology. Regulatory, integrative and comparative physiology JO - Am. J. Physiol. Regul. Integr. Comp. Physiol. VL - 300 IS - 6 N2 - Interactions between neurosteroids and GABA receptors have attracted particular attention in the supraoptic nucleus (SON). Although GABA(A) receptors (GABA(A)R) mediate a sustained tonic inhibitory current (I(tonic)), as well as conventional phasic inhibitory postsynaptic currents (IPSCs, I(phasic)) in the SON, whether the steroid modulation on I(tonic) is present in SON magnocelluar neurosecretory cells (MNCs) is unknown. Here, we addressed this question and gained insights into the potential molecular configuration of GABA(A) receptors mediating I(tonic) and conferring its neurosteroids sensitivity in SON MNCs. 4,5,6,7-tetrahydroisoxazolo[5,4-c]-pyridin-3-ol (THIP) (1 μM), a relatively selective extrasynaptic GABA(A)R agonist, facilitated I(tonic) without affecting the main characteristics of IPSCs, while DS-2, a relatively selective modulator of GABA(A)R δ-subunits, caused minimal changes in I(tonic) of SON MNCs. l-655,708, a relatively selective GABA(A)R α(5)-subunit inverse agonist, blocked ∼35% of the total I(tonic) both under basal and elevated ambient GABA concentration (3 μM). Facilitation of I(tonic) by benzodiazepines further supported the role of GABA(A)R γ(2)-subunit in I(tonic) of SON MNCs. Quantitative RT-PCR analysis showed much lesser expression of GABA(A)R δ-subunit than the α(5) or γ(2)-subunit in the SON. Allopregnanolone and 3α,5α-tetrahydrodeoxycorticosterone increased both I(tonic) and I(phasic) in SON MNCs, respectively, although more than 90% of the current increase was mediated by I(tonic) during the neurosteroid facilitation. Finally, l-655,708 attenuated the neurosteroid facilitation of I(tonic) but not of I(phasic). Altogether, our results suggest that I(tonic), mediated mainly by benzodiazepine-sensitive GABA(A)Rs containing α(5)-, β-, and γ(2)-, and to a lesser extent, δ-subunits, is a potential target of neurosteroid modulation in SON neurons. SN - 1522-1490 UR - https://www.unboundmedicine.com/medline/citation/21451144/Neurosteroid_modulation_of_benzodiazepine_sensitive_GABAA_tonic_inhibition_in_supraoptic_magnocellular_neurons_ L2 - https://journals.physiology.org/doi/10.1152/ajpregu.00627.2010?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -