High extracellular potassium modulates nitric oxide synthase expression in human astrocytes.
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 KCI on astrocyte iNOS expression. The results demonstrate that KCI at 25-75 mM potently inhibits astrocyte nitrite production stimulated by interleukin-1 (IL-1)/interferon-gamma (IFNgamma). 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/IFNgamma. 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.
Morgan
A C
AC
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Chang
H Y
HY
Liu
J S
JS
Hua
L L
LL
Lee
S C
SC
D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism*; D005333:Fetus / Q000378:metabolism; D006801:Humans; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors
D009573:Nitrites; D015221:Potassium Channels; D012333:RNA, Messenger; D012965:Sodium Chloride; D011189:Potassium Chloride; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II