Chronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat.

TitleChronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat.
Publication TypeJournal Article
Year of Publication2011
AuthorsKim, JS, Kim WB, Kim Y-B, Lee Y, Kim YS, Shen F-Y, Lee SW, Park D, Choi H-J, Hur J, Park JJ, Han HC, Colwell CS, Cho Y-W, Kim YI
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Date Published2011 Sep 14
KeywordsAction Potentials, Animals, Bicuculline, Bumetanide, Electric Stimulation, gamma-Aminobutyric Acid, hypothalamus, Male, Neural Inhibition, Neurons, Osmotic Pressure, Oxytocin, Patch-Clamp Techniques, Rats, Rats, Sprague-Dawley, Sodium, Sodium Potassium Chloride Symporter Inhibitors, Sodium-Potassium-Chloride Symporters, Stress, Physiological, Vasopressins

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.

Alternate JournalJ. Neurosci.