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

Jeong Sook Kim, Woong Bin Kim, Young Beom Kim, Yeon Lee, Yoon Sik Kim, Feng Yan Shen, Seung Won Lee, Dawon Park, Hee Joo Choi, Jinyoung Hur, Joong Jean Park, Hee Chul Han, Christopher S. Colwell, Young Wuk Cho, Yang In Kim

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)


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 GABAA 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.

Original languageEnglish
Pages (from-to)13312-13322
Number of pages11
JournalJournal of Neuroscience
Issue number37
Publication statusPublished - 2011 Sept 14

ASJC Scopus subject areas

  • General Neuroscience


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