PMID- 12532279 OWN - NLM STAT- MEDLINE DCOM- 20030930 LR - 20161124 IS - 0022-2631 (Print) IS - 0022-2631 (Linking) VI - 191 IP - 1 DP - 2003 Jan 1 TI - Hepatocyte growth factor/scatter factor stimulates Ca2+-activated membrane K+ current and migration of MDCK II cells. PG - 77-86 AB - 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. FAU - Jin, M AU - Jin M AD - Department of Physiology, James H. Quillen College of Medicine, East Tennessee State University, PO Box 70,576, Johnson City, TN 37614, USA. FAU - Defoe, D M AU - Defoe DM FAU - Wondergem, R AU - Wondergem R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Membr Biol JT - The Journal of membrane biology JID - 0211301 RN - 0 (Marine Toxins) RN - 0 (Peptides) RN - 0 (Potassium Channels, Calcium-Activated) RN - 115422-61-2 (Charybdotoxin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 773HER9B6T (iberiotoxin) RN - G07GZ97H65 (Clotrimazole) SB - IM MH - Animals MH - Cell Line MH - Cell Movement/drug effects/*physiology MH - Charybdotoxin/pharmacology MH - Clotrimazole/pharmacology MH - Dogs MH - Epithelium/*drug effects/*physiology/ultrastructure MH - Hepatocyte Growth Factor/*pharmacology MH - Ion Channel Gating/drug effects/physiology MH - Kidney/drug effects/physiology/ultrastructure MH - Marine Toxins/pharmacology MH - Membrane Potentials/drug effects/physiology MH - Peptides/pharmacology MH - Potassium Channels, Calcium-Activated/*drug effects/*physiology EDAT- 2003/01/18 04:00 MHDA- 2003/10/01 05:00 CRDT- 2003/01/18 04:00 PHST- 2002/04/19 00:00 [received] PHST- 2003/01/18 04:00 [pubmed] PHST- 2003/10/01 05:00 [medline] PHST- 2003/01/18 04:00 [entrez] AID - 10.1007/s00232-002-1045-1 [doi] PST - ppublish SO - J Membr Biol. 2003 Jan 1;191(1):77-86. doi: 10.1007/s00232-002-1045-1.