High extracellular potassium modulates nitric oxide synthase expression in human astrocytes

Anna C.A. Morgan, Hee Yoon Chang, Judy S.H. Liu, Liwei L. Hua, Sunhee C. Lee

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Inducible nitric oxide synthase (iNOS) is a molecule of great interest, given the numerous biological activities of nitric oxide and the documented expression of iNOS in several CNS pathologies. There also appears to be species-dependent regulation of iNOS expression as well as CNS-specific regulation. In this study, we have examined cultures of cytokine-activated primary human astrocytes as a model system with which to study the mechanisms of iNOS regulation in human CNS. As one of the major functions of astrocytes is spatial buffering of K+ ion, we examined the effect of high extracellular KCl on astrocyte iNOS expression. The results demonstrate that KCl at 25-75 mM potently inhibits astrocyte nitrite production stimulated by interleukin-1 (IL-1)/interferon-γ (IFNγ). In addition, several potassium channel inhibitors such as CsCl, tetraethylammonium, and 4-aminopyridine as well as nigericin inhibited astrocyte iNOS expression induced by IL-1/IFNγ. These results demonstrate a novel role for astrocyte potassium channel activity in modulation of astrocyte function. They further suggest neural-specific mechanisms for glial iNOS regulation.

Original languageEnglish (US)
Pages (from-to)1903-1912
Number of pages10
JournalJournal of Neurochemistry
Volume74
Issue number5
DOIs
StatePublished - May 3 2000

Keywords

  • Brain
  • Cytokine
  • Hyperkalemia
  • Inflammation
  • Interleukin-1
  • Osmolarity

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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