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High Extracellular Potassium Modulates Nitric Oxide Synthase Expression in Human Astrocytes
Author(s) -
Morgan Anna C. A.,
Chang HeeYoon,
Liu Judy S. H.,
Hua Liwei L.,
Lee Sunhee C.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741903.x
Subject(s) - nitric oxide synthase , extracellular , neuronal nitric oxide synthase , nitric oxide , microbiology and biotechnology , chemistry , neuroscience , biochemistry , biology , enzyme , endocrinology
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 m M 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.