RT Journal Article
SR Electronic
T1 Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13312
OP 13322
DO 10.1523/JNEUROSCI.1440-11.2011
VO 31
IS 37
A1 Jeong Sook Kim
A1 Woong Bin Kim
A1 Young-Beom Kim
A1 Yeon Lee
A1 Yoon Sik Kim
A1 Feng-Yan Shen
A1 Seung Won Lee
A1 Dawon Park
A1 Hee-Joo Choi
A1 Jinyoung Hur
A1 Joong Jean Park
A1 Hee Chul Han
A1 Christopher S. Colwell
A1 Young-Wuk Cho
A1 Yang In Kim
YR 2011
UL http://www.jneurosci.org/content/31/37/13312.abstract
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 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 (EGABA) in MNCs. This EGABA 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 GABAA 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.