Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats

Evgeniy S. Potapenko, Vinicia C. Biancardi, Yiqiang Zhou, Javier E. Stern

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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 (μM dihydrokainate (DHK)], resulted in a persistent N-methyl-D-aspartate receptor (NMDAR)-mediated inward current (tonic Inmda) 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 (μM TBOA) evoked an enhanced tonic Inmda 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.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number3
DOIs
StatePublished - Aug 1 2012

Fingerprint

Amino Acid Transport System X-AG
Astrocytes
Heart Failure
Neurons
Supraoptic Nucleus
Glutamic Acid
Neuroglia
Electrophysiology
N-Methyl-D-Aspartate Receptors
Vasopressins
Neurotransmitter Agents
Proteins
Cell Membrane
Pharmacology
Morbidity

Keywords

  • Extrasynaptic
  • GLAST
  • GLT1
  • N-methyl-D-aspartate
  • Supraoptic

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Altered astrocyte glutamate transporter regulation of hypothalamic neurosecretory neurons in heart failure rats. / Potapenko, Evgeniy S.; Biancardi, Vinicia C.; Zhou, Yiqiang; Stern, Javier E.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 303, No. 3, 01.08.2012, p. 291-300.

Research output: Contribution to journalArticle

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