OSCILLATING ACTIVITY OF A CA2-SENSITIVE K+ CHANNEL - A PREREQUISITE FOR MIGRATION OF TRANSFORMED MADIN-DARBY CANINE KIDNEY FOCUS CELLS()

Migration plays an important role in the formation of tumor metastases . Nonetheless, little is known about electrophysiological phenomena ac companying or underlying migration. Previously, we had shown that in m igrating alkali-transformed Madin-Darby canine kidney focus (MDCK-F) c ells a Ca2+ sensitive 53-pS K+ channel underlies oscillations of the c ell membrane potential. The present study defines the role this channe l plays in migration of MDCK-F cells. We monitored migration of indivi dual MDCK-F cells by video imaging techniques. Under control condition s, MDCK-F cells migrated at a rate of 0.90+/-0.03 mu m/min (n = 201). Application of K+ channel blockers(1 and 5 mmol/liter Ba2+, 5 mmol/lit er tetraethyl-ammonium, 100 mu mol/liter 4-aminopyridine, 5 nmol/liter charybdotoxin) caused marked inhibition of migration, pointing to the importance of K+ channels in migration. Using patch-clamp techniques, we demonstrated the sensitivity of the Ca2+ sensitive 53-pS K+ channe l to these blockers. Blockade of this K+ channel and inhibition of mig ration were closely correlated, indicating the necessity of oscillatin g K+ channel activity for migration. Migration of MDCK-F cells was als o inhibited by furosemide or bumetanide, blockers of the Na+/K+/2Cl(-) co-transporter. We present a model for migration in which oscillation s of cell volume play a central role. Whenever they are impaired, migr ation is inhibited.