Expression of Kv1.2 in microglia and its putative roles in modulating production of proinflammatory cytokines and reactive oxygen species.
Microglial cells are endowed with different potassium ion channels but their expression and specific functions have remained to be fully clarified. This study has shown Kv1.2 expression in the amoeboid microglia in the rat brain between 1 (P1) and 10 (P10) days of age. Kv1.2 expression was localized in the ramified microglia at P14 and was hardly detected at P21. In postnatal rats exposed to hypoxia, Kv1.2 immunoreactivity in microglia was markedly enhanced. Quantitative RT-PCR analysis confirmed Kv1.2 mRNA expression in microglial cells in vitro. It was further shown that Kv1.2 and protein expression coupled with that of interleukin 1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) was significantly increased when the cells were subjected to hypoxia. The same increase was observed in cells exposed to adenosine 5'-triphosphate (ATP) and lipopolysaccharide (LPS). Concomitantly, the intracellular potassium concentration decreased significantly. Blockade of Kv1.2 channel with rTityustoxin-Kalpha (TsTx) resulted in partial recovery of intracellular potassium concentration accompanied by a reduced expression of IL-1beta and TNF-alpha mRNA and protein expression and intracellular reactive oxygen species (ROS) production. We conclude that Kv1.2 in microglia modulates IL-1beta and TNF-alpha expression and ROS production probably by regulating the intracellular potassium concentration.
Li
Fan
F
Faculty of Basic Medical Sciences, Kunming Medical College, Kunming, China.
Lu
Jia
J
Wu
Chun-Yun
CY
Kaur
Charanjit
C
Sivakumar
Viswanathan
V
Sun
Jun
J
Li
Shuqing
S
Ling
Eng-Ang
EA
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D051663:Kv1.2 Potassium Channel / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress / Q000276:immunology*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D051663:Kv1.2 Potassium Channel; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000255:Adenosine Triphosphate; D011188:Potassium