Hepatocyte Growth Factor/Scatter Factor Stimulates Ca 2+-Activated Membrane K+ Current and Migration of MDCK II Cells
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates migration of various cells and has been linked via Met tyrosine kinase-signaling to transformation and the metastatic phenotype. Migration of transformed MDCK-F cells depends on activation of a charybdotoxin-sensitive, volume-activated membrane K+ current. Thus, we used patchclamp electrophysiology and transwell migration assays to determine whether HGF/SF stimulation of MDCK II cell migration depends on the activation of membrane K+ currents. HGF/SF activated a membrane K+ current that increased over 24 hr, and which could be modulated by increasing intracellular calcium concentration, [Ca2+]i. Charybdotoxin (ChTX, 50 nM), iberiotoxin (IbTX, 100 nM), stichodactyla toxin (Stk, 100 nM) and clotrimazole (CLT, 1 μM) all inhibited this current. HGF/SF (100 scatter units/ml) significantly increased MDCK II cell migration over 8 hr compared to control cells. Addition of ChTX (50 nM), IbTX (100 nm), Stk (100 nM) or CLT (1 μM) inhibited the HGF/SF-stimulated MDCK II cell migration. We conclude that the activation of membrane Ca2+-activated K+ current is necessary for HGF/ SF stimulation of MDCK II cell.
Jin, M.; Defoe, D. M.; and Wondergem, R.. 2003. Hepatocyte Growth Factor/Scatter Factor Stimulates Ca 2+-Activated Membrane K+ Current and Migration of MDCK II Cells. Journal of Membrane Biology. Vol.191(1). 77-86. https://doi.org/10.1007/s00232-002-1045-1 PMID: 12532279 ISSN: 0022-2631