Kupffer cells contain a glycine-gated chloride channel.
Here the effect of glycine on intracellular Ca2+ concentration ([Ca2+]i) in cultured Kupffer cells stimulated with lipopolysaccharide (LPS) was investigated to assess the possibility that they contain a glycine-gated chloride channel. LPS (10 micrograms/ml) increased [Ca2+]i rapidly, with peak values reaching 307 +/- 29 nM. Glycine (1 mM) prevented this increase nearly completely. Low concentrations of strychnine (1 microM), a glycine receptor antagonist, reversed the inhibitory effect of glycine completely; however, high concentrations of strychnine (1 mM) mimicked glycine. The effects of glycine and high-dose strychnine were prevented when cells were incubated in chloride-free buffer. Furthermore, potassium (25 mM) and LPS depolarized the Kupffer cell plasma membrane, whereas glycine caused hyperpolarization and prevented depolarization due to potassium and LPS. Moreover, tumor necrosis factor-alpha (TNF-alpha) production in cultured Kupffer cells due to LPS was decreased significantly by glycine. Therefore, it is concluded that Kupffer cells contain a glycine-gated chloride channel similar to that described previously in the central nervous system. Prevention of increases in [Ca2+]i due to LPS by activation of chloride influx reduced synthesis and release of toxic mediators by Kupffer cells.
Ikejima
K
K
Department of Pharmacology, University of North Carolina at Chapel Hill 27599-7365, USA.
Qu
W
W
Stachlewitz
R F
RF
Thurman
R G
RG
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D004926:Escherichia coli; D005260:Female; D005998:Glycine / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007728:Kupffer Cells / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D008070:Lipopolysaccharides; D013331:Strychnine; D002118:Calcium; D005998:Glycine