PMID- 22696576 OWN - NLM STAT- MEDLINE DCOM- 20121016 LR - 20211021 IS - 1522-1490 (Electronic) IS - 0363-6119 (Print) IS - 0363-6119 (Linking) VI - 303 IP - 3 DP - 2012 Aug 1 TI - Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats. PG - R291-300 LID - 10.1152/ajpregu.00056.2012 [doi] AB - Neurohumoral activation, which includes augmented plasma levels of the neurohormone vasopressin (VP), is a common finding in heart failure (HF) that contributes to morbidity and mortality in this disease. While an increased activation of magnocellular neurosecretory cells (MNCs) and enhanced glutamate function in HF is well documented, the precise underlying mechanisms remain to be elucidated. Here, we combined electrophysiology and protein measurements to determine whether altered glial glutamate transporter function and/or expression occurs in the hypothalamic supraoptic nucleus (SON) during HF. Patch-clamp recordings obtained from MNCs in brain slices show that pharmacological blockade of astrocyte glutamate transporter 1 (GLT1) function [500 muM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic I(NMDA)) in sham rats, an effect that was significantly smaller in MNCs from HF rats. In addition, we found a diminished GLT1 protein content in plasma membrane (but not cytosolic) fractions of SON punches in HF rats. Conversely, astrocyte GLAST expression was significantly higher in the SON of HF rats, while nonselective blockade of glutamate transport activity (100 muM TBOA) evoked an enhanced tonic I(NMDA) activation in HF rats. Steady-state activation of NMDARs by extracellular glutamate levels was diminished during HF. Taken together, these results support a shift in the relative expression and function of two major glial glutamate transporters (from GLT1 to GLAST predominance) during HF. This shift may act as a compensatory mechanism to preserve an adequate basal glutamate uptake level in the face of an enhanced glutamatergic afferent activity in HF rats. FAU - Potapenko, Evgeniy S AU - Potapenko ES AD - Department of Physiology, Georgia Health Sciences University, Augusta, 30912, USA. FAU - Biancardi, Vinicia C AU - Biancardi VC FAU - Zhou, Yiqiang AU - Zhou Y FAU - Stern, Javier E AU - Stern JE LA - eng GR - R01 HL090948/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120613 PL - United States TA - Am J Physiol Regul Integr Comp Physiol JT - American journal of physiology. Regulatory, integrative and comparative physiology JID - 100901230 RN - 0 (Excitatory Amino Acid Transporter 1) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Slc1a2 protein, rat) RN - 0 (Slc1a3 protein, rat) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Disease Models, Animal MH - Excitatory Amino Acid Transporter 1/metabolism MH - Excitatory Amino Acid Transporter 2/*metabolism MH - Heart Failure/*metabolism/pathology MH - Hypothalamus, Anterior/*metabolism/pathology MH - Male MH - Neurons/*metabolism/pathology MH - Patch-Clamp Techniques MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/metabolism PMC - PMC3423986 EDAT- 2012/06/15 06:00 MHDA- 2012/10/17 06:00 PMCR- 2013/08/01 CRDT- 2012/06/15 06:00 PHST- 2012/06/15 06:00 [entrez] PHST- 2012/06/15 06:00 [pubmed] PHST- 2012/10/17 06:00 [medline] PHST- 2013/08/01 00:00 [pmc-release] AID - ajpregu.00056.2012 [pii] AID - R-00056-2012 [pii] AID - 10.1152/ajpregu.00056.2012 [doi] PST - ppublish SO - Am J Physiol Regul Integr Comp Physiol. 2012 Aug 1;303(3):R291-300. doi: 10.1152/ajpregu.00056.2012. Epub 2012 Jun 13.