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 language||English (US)|
|Number of pages||10|
|Journal||Journal of Neurochemistry|
|State||Published - May 3 2000|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience