PMID- 24313753 OWN - NLM STAT- MEDLINE DCOM- 20150110 LR - 20140116 IS - 1365-2826 (Electronic) IS - 0953-8194 (Linking) VI - 26 IP - 1 DP - 2014 Jan TI - Attenuated benzodiazepine-sensitive tonic GABAA currents of supraoptic magnocellular neuroendocrine cells in 24-h water-deprived rats. PG - 26-34 LID - 10.1111/jne.12123 [doi] AB - In supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs), gamma-GABA, via activation of GABAA receptors (GABAA Rs), mediates persistent tonic inhibitory currents (Itonic ), as well as conventional inhibitory postsynaptic currents (IPSCs, Iphasic ). In the present study, we examined the functional significance of Itonic in SON MNCs challenged by 24-h water deprivation (24WD). Although the main characteristics of spontaneous IPSCs were similar in 24WD compared to euhydrated (EU) rats, Itonic , measured by bicuculline (BIC)-induced Iholding shifts, was significantly smaller in 24WD compared to EU rats (P < 0.05). Propofol and diazepam prolonged IPSC decay time to a similar extent in both groups but induced less Itonic in 24WD compared to EU rats, suggesting a selective decrease in GABAA receptors mediating Itonic over Iphasic in 24WD rats. THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential delta subunit agonist, and L-655,708, a GABAA receptor alpha5 subunit selective imidazobenzodiazepine, caused a significantly smaller inward and outward shift in Iholding , respectively, in 24WD compared to EU rats (P < 0.05 in both cases), suggesting an overall decrease in the alpha5 subunit-containing GABAA Rs and the delta subunit-containing receptors mediating Itonic in 24WD animals. Consistent with a decrease in 24WD Itonic , bath application of GABA induced significantly less inhibition of the neuronal firing activity in 24WD compared to EU SON MNCs (P < 0.05). Taken together, the results of the present study indicate a selective decrease in GABAA Rs functions mediating Itonic as opposed to those mediating Iphasic in SON MNCs, demonstrating the functional significance of Itonic with respect to increasing neuronal excitability and hormone secretion in 24WD rats. CI - (c) 2014 British Society for Neuroendocrinology. FAU - Pandit, S AU - Pandit S AD - Department of Physiology, School of Medicine, Brain Research Institute, Chungnam National University, Jung-gu, Daejeon, Korea. FAU - Song, J G AU - Song JG FAU - Kim, Y J AU - Kim YJ FAU - Jeong, J A AU - Jeong JA FAU - Jo, J Y AU - Jo JY FAU - Lee, G S AU - Lee GS FAU - Kim, H-W AU - Kim HW FAU - Jeon, B H AU - Jeon BH FAU - Lee, J U AU - Lee JU FAU - Park, J B AU - Park JB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neuroendocrinol JT - Journal of neuroendocrinology JID - 8913461 RN - 0 (GABA Agonists) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Hypnotics and Sedatives) RN - 0 (Imidazoles) RN - 0 (Isoxazoles) RN - 0 (L 655,708) RN - 0 (Protein Subunits) RN - 0 (Receptors, GABA-A) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - K1M5RVL18S (gaboxadol) RN - Q3JTX2Q7TU (Diazepam) RN - Y37615DVKC (Bicuculline) RN - YI7VU623SF (Propofol) SB - IM MH - Animals MH - Bicuculline/pharmacology MH - Diazepam/pharmacology MH - GABA Agonists/pharmacology MH - GABA-A Receptor Antagonists/pharmacology MH - Hypnotics and Sedatives/pharmacology MH - Imidazoles/pharmacology MH - Inhibitory Postsynaptic Potentials/drug effects/*physiology MH - Isoxazoles/pharmacology MH - Male MH - Neuroendocrine Cells/drug effects/*physiology MH - Propofol/pharmacology MH - Protein Subunits/drug effects/physiology MH - Rats MH - Receptors, GABA-A/*physiology MH - Supraoptic Nucleus/*cytology/drug effects/*physiology MH - Water Deprivation/*physiology MH - gamma-Aminobutyric Acid/pharmacology OTO - NOTNLM OT - oxytocin OT - supraoptic nucleus OT - tonic GABAA current OT - vasopressin OT - water deprivation EDAT- 2013/12/10 06:00 MHDA- 2015/01/13 06:00 CRDT- 2013/12/10 06:00 PHST- 2013/04/30 00:00 [received] PHST- 2013/11/05 00:00 [revised] PHST- 2013/12/01 00:00 [accepted] PHST- 2013/12/10 06:00 [entrez] PHST- 2013/12/10 06:00 [pubmed] PHST- 2015/01/13 06:00 [medline] AID - 10.1111/jne.12123 [doi] PST - ppublish SO - J Neuroendocrinol. 2014 Jan;26(1):26-34. doi: 10.1111/jne.12123.