Depolarization of cultured astrocytes by leukotriene B4. Evidence for the induction of a K+ conductance inhibitor.
Since astrocytes have been shown to participate in intracerebral immunological processes we investigated the effect of the immune mediators, leukotrienes (LT) B4, LTC4 and LTD4 on membrane properties of cultured astrocytes from neonatal rat brain. When LTB4 was added to the bath solution the membrane potential slowly decreased from -96 mV to -38 mV. While LTB4 at a concentration of 500 nM was ineffective, depolarization occurred when concentrations of 750 nM and above were used. The depolarizing effect was specific for LTB4, since LTC4 and LTD4, other arachidonic acid derivates, failed to depolarize astrocytes at even higher concentrations (1 microM). When the K+ conductance blocker, Ba2+ (2 mM), was added to the bath solution, astrocytes depolarized to the same degree but no further depolarization was achieved when LTB4 was added. Bath application of Co2+ (1 mM), in order to reduce putative Ca2+ inward currents or reduced internal chloride concentration, did not alter the LTB4-induced depolarization, thus arguing against additional Ca(2+)- or Cl(-)-dependent depolarizing effects. The LTB4-induced depolarization could be markedly reduced, however, by preincubation of the cells with cycloheximide (2 microM), which blocks translation and thereby protein synthesis. Cycloheximide alone had no effect on the membrane potential. These data indicate that, in astrocytes, LTB4 stimulates the synthesis of a protein, which, in turn, inhibits K+ conductances. This effect could impair glial, as well as neuronal, functions during CNS diseases accompanied by immunological processes.
Department of Neurology, Heinrich-Heine University, Düsseldorf, Germany.
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H
Köller
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M
Siebler
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M
Pekel
H W
HW
Müller
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004594:Electrophysiology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013189:SRS-A / Q000494:pharmacology
D002712:Chlorides; D009419:Nerve Tissue Proteins; D009467:Neuromuscular Depolarizing Agents; D015221:Potassium Channels; D013189:SRS-A; D007975:Leukotriene B4; D003035:Cobalt; D003513:Cycloheximide