Hepatocyte growth factor/scatter factor stimulates Ca2+-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 patch-clamp 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 mM) 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 microM) 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.
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Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70,576, Johnson City, TN 37614, USA.
Defoe
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Wondergem
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D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D004285:Dogs; D004848:Epithelium / Q000187:drug effects* / Q000502:physiology* / Q000648:ultrastructure; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D008387:Marine Toxins / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects* / Q000502:physiology*
D008387:Marine Toxins; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; D017228:Hepatocyte Growth Factor; C064719:iberiotoxin; D003022:Clotrimazole