title: Chronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat.
abstract: 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.
authors.affiliation: Department of Physiology, Biomedical Science Institute and Brain Korea 21 Project Center, Kyung Hee University School of Medicine, Seoul 130-701, South Korea.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Kim
authors.forename: Woong Bin
authors.initials: WB
authors.lastname: Kim
authors.forename: Young-Beom
authors.initials: YB
authors.lastname: Kim
authors.forename: Yeon
authors.initials: Y
authors.lastname: Lee
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.forename: Feng-Yan
authors.initials: FY
authors.lastname: Shen
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Dawon
authors.initials: D
authors.lastname: Park
authors.forename: Hee-Joo
authors.initials: HJ
authors.lastname: Choi
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Hur
authors.forename: Joong Jean
authors.initials: JJ
authors.lastname: Park
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Han
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Colwell
authors.forename: Young-Wuk
authors.initials: YW
authors.lastname: Cho
authors.forename: Yang In
authors.initials: YI
authors.lastname: Kim
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009997:Osmotic Pressure / Q000502:physiology*; D010121:Oxytocin / Q000097:blood / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis; D064506:Solute Carrier Family 12, Member 2; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000097:blood / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D014667:Vasopressins; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D001640:Bicuculline