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Mechanisms of Water Deprivation‐Induced Enhancement of Glutamatergic Activity in the Hypothalamic Paraventricular Nucleus (PVN)
Author(s) -
Bardgett Megan,
Baumgartner Anne D.,
Calderon Alfredo S.,
Toney Glenn M.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.901.1
Subject(s) - nmda receptor , glutamatergic , medicine , endocrinology , glutamate receptor , chemistry , blockade , receptor
Evidence indicates that NMDA receptor “tone” in the PVN of 48 h water deprived (WD) rats is increased compared to euhydrated (EU) controls. Consistent with this, acute blockade of PVN NMDAR reduces sympathetic nerve activity (SNA) & mean arterial pressure (MAP) in WD rats, but has little effect in EU rats. Wet weight & water content of brain were determined to be nearly identical in EU & WD rats (n=5, P>0.9), suggesting that increased PVN NMDAR tone in WD rats is unlikely to result from increased L‐glutamate concentration arising from brain dehydration and ECF volume contraction. Next, we determined in anesthetized rats that bilateral PVN injection of the glutamate transporter blocker TBOA (250 pmol in 50 nl) evoked greater increases of renal SNA & MAP in EU than WD rats (RSNA: 26±4 % vs 15±2 %, P<0.05; MAP: 15±1 mmHg vs 7±1 mmHg, P<0.001). In whole cell voltage‐clamp recordings (Vhold: −60 mV) from PVN‐RVLM neurons in brains slices, TBOA (100 μM) likewise elicited greater inward current (P<0.05) in the EU (−144±21 pA, n=3) than WD (−40±10 pA, n=5) group. Both in vivo & in vitro TBOA evoked responses were abrogated by NMDAR blockade with AP 5 . We conclude that greater functional NMDAR tone in the PVN of WD rats may not simply reflect increased glutamatergic synaptic input, but instead involve increased PVN neuronal responsiveness to L‐glutamate or reduced ongoing L‐glutamate uptake, or both. Support: HL102310 & HL 088052 (GMT)