Abstract
Deactivation of brain macrophages (microglia) by transforming growth factor-β (TGF-β) is characterized by enhanced Kv1.3 K+ channel expression. The intracellular mechanisms by which TGF-β causes K+ channel upregulation in microglia have remained unclear. We show here that the protein kinase inhibitor H7 abolishes TGF-β-induced increases in delayed rectifier K+ current density. However, this effect cannot be related to inhibition of protein kinase C (PKC) or protein kinase A (PKA) activity, because specific PKC and PKA inhibitors did not exhibit effects identical to H7. TGF-β-induced Kv1.3 channel expression was also unaffected by inhibitors of tyrosine kinase, Ca2+/calmodulin kinase II and mitogen-activated protein (MAP) kinase ERK. In contrast, delayed rectifier K+ current density was larger in TGF-β-stimulated cells pretreated with the p38 MAP kinase inhibitor SB203580 or the phosphatidylinositol 3-OH (PI3) kinase inhibitor wortmannin, suggesting that both p38 MAP kinase and PI3 kinase regulate negatively the upregulation of Kv1.3 K+ channels in TGF-β-treated microglial cells.
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Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft grant SFB 507/C7 and a Heisenberg fellowship (both to C.E.). The authors wish to thank Sieglinde Latta for the preparation of cell cultures.
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Schilling, T., Eder, C. Effects of kinase inhibitors on TGF-β induced upregulation of Kv1.3 K+ channels in brain macrophages. Pflugers Arch - Eur J Physiol 447, 312–315 (2003). https://doi.org/10.1007/s00424-003-1155-3
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DOI: https://doi.org/10.1007/s00424-003-1155-3