PMID- 21917814 OWN - NLM STAT- MEDLINE DCOM- 20111122 LR - 20211020 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 31 IP - 37 DP - 2011 Sep 14 TI - Chronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat. PG - 13312-22 LID - 10.1523/JNEUROSCI.1440-11.2011 [doi] AB - In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA(A) receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E(GABA)) in MNCs. This E(GABA) shift was associated with increased expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA(A) receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl(-) gradients. FAU - Kim, Jeong Sook AU - Kim JS AD - Department of Physiology, Biomedical Science Institute and Brain Korea 21 Project Center, Kyung Hee University School of Medicine, Seoul 130-701, South Korea. FAU - Kim, Woong Bin AU - Kim WB FAU - Kim, Young-Beom AU - Kim YB FAU - Lee, Yeon AU - Lee Y FAU - Kim, Yoon Sik AU - Kim YS FAU - Shen, Feng-Yan AU - Shen FY FAU - Lee, Seung Won AU - Lee SW FAU - Park, Dawon AU - Park D FAU - Choi, Hee-Joo AU - Choi HJ FAU - Hur, Jinyoung AU - Hur J FAU - Park, Joong Jean AU - Park JJ FAU - Han, Hee Chul AU - Han HC FAU - Colwell, Christopher S AU - Colwell CS FAU - Cho, Young-Wuk AU - Cho YW FAU - Kim, Yang In AU - Kim YI LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Slc12a2 protein, rat) RN - 0 (Sodium Potassium Chloride Symporter Inhibitors) RN - 0 (Sodium-Potassium-Chloride Symporters) RN - 0 (Solute Carrier Family 12, Member 2) RN - 0Y2S3XUQ5H (Bumetanide) RN - 11000-17-2 (Vasopressins) RN - 50-56-6 (Oxytocin) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - 9NEZ333N27 (Sodium) RN - Y37615DVKC (Bicuculline) SB - IM MH - Action Potentials/drug effects/physiology MH - Animals MH - Bicuculline/pharmacology MH - Bumetanide/pharmacology MH - Electric Stimulation/methods MH - Hypothalamus/drug effects/metabolism/physiology MH - Male MH - Neural Inhibition/*physiology MH - Neurons/*physiology MH - Osmotic Pressure/*physiology MH - Oxytocin/blood/physiology MH - Patch-Clamp Techniques MH - Rats MH - Rats, Sprague-Dawley MH - Sodium/metabolism MH - Sodium Potassium Chloride Symporter Inhibitors/pharmacology MH - Sodium-Potassium-Chloride Symporters/biosynthesis MH - Solute Carrier Family 12, Member 2 MH - Stress, Physiological/drug effects/*physiology MH - Vasopressins/blood/*physiology MH - gamma-Aminobutyric Acid/*physiology PMC - PMC6623275 EDAT- 2011/09/16 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/03/14 CRDT- 2011/09/16 06:00 PHST- 2011/09/16 06:00 [entrez] PHST- 2011/09/16 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/03/14 00:00 [pmc-release] AID - 31/37/13312 [pii] AID - 3720696 [pii] AID - 10.1523/JNEUROSCI.1440-11.2011 [doi] PST - ppublish SO - J Neurosci. 2011 Sep 14;31(37):13312-22. doi: 10.1523/JNEUROSCI.1440-11.2011.