Expression and function of outward K+ channels induced by lipopolysaccharide in microglia.
Cultured microglia exposed to lipopolysaccharide (LPS) express outward K+ currents. These currents are due to the expression of new K+ channels detected by antibodies against Kv1.5, a shaker type delayed rectifier. We examined whether the K+ currents are involved in microglial activation. The amount of nitrite, converted from nitric oxide (NO), was measured as an indication of microglial activation [Chao, C. C., Hu, S., Molitor, T. W., Shaskan, E. G., and Peterson, P. K. (1992) J. Immunol. 149, 2730-2741]. Nitrite was detected starting from 24 h after LPS treatment and continuously increased over 4 days. Contrary to this, in the presence of 4-aminopyridine (4-AP, 2 mM), a blocker of outward K+ currents, nitrite production was reduced to less than 50%. However, the treatment of 4-AP 24 h after LPS did not reduce nitrite production. Other K+ channel blockers having a less blocking effect on outward K+ currents, such as 5 mM tetraethylammonium (TEA) and 1 mM Cs+, had little effect. The present study shows that the outward K+ channels induced by LPS are immunologically related to Kv1.5 and also suggests that these channels are required for microglial activation, particularly for the initiation of the activation process.
Pyo
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H
Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea.
Chung
S
S
Jou
I
I
Gwag
B
B
Joe
E H
EH
D000818:Animals; D000906:Antibodies; D002540:Cerebral Cortex; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D015221:Potassium Channels / Q000032:analysis / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D000906:Antibodies; C496983:Kcna5 protein, rat; D051666:Kv1.5 Potassium Channel; D008070:Lipopolysaccharides; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D009569:Nitric Oxide