Oscillating activity of a Ca(2+)-sensitive K+ channel. A prerequisite for migration of transformed Madin-Darby canine kidney focus cells.

Abstract

Migration plays an important role in the formation of tumor metastases. Nonetheless, little is known about electrophysiological phenomena accompanying or underlying migration. Previously, we had shown that in migrating alkali-transformed Madin-Darby canine kidney focus (MDCK-F) cells a Ca+-sensitive 53-pS K+ channel underlies oscillations of the cell membrane potential. The present study defines the role this channel plays in migration of MDCK-F cells. We monitored migration of individual MDCK-F cells by video imaging techniques. Under control conditions, MDCK-F cells migrated at a rate of 0.90±0.03 Mim/min (n = 201). Application of K+ channel blockers ( 1 and 5 mmol / liter Ba2+, 5 mmol /liter tetraethylammonium, 100 ,mol/liter 4-aminopyridine, 5 nmol/liter charybdotoxin) caused marked inhibition of migration, pointing to the importance of K+ channels in migration. Using patchclamp techniques, we demonstrated the sensitivity of the Ca2+-sensitive 53-pS K+ channel to these blockers. Blockade of this K+ channel and inhibition of migration were closely correlated, indicating the necessity of oscillating K+ channel activity for migration. Migration of MDCK-F cells was also inhibited by furosemide or bumetanide, blockers of the Na+/K+/2Cl-cotransporter. We present a model for migration in which oscillations of cell volume play a central role. Whenever they are impaired, migration is inhibited. (J. Clin. Invest. 1994.

Eag1 and Bestrophin 1 Are Up-regulated in Fast-growing Colonic Cancer Cells

“…These fast-growing cells express Ca 2ϩ -activated K ϩ channels that largely enhance cell migration (23). The fastgrowing T 84 cells described in the present study showed a strong increase in the expression of the Best1 Cl Ϫ channel along with Eag1 potassium channels.…”

Migration-associated secretion of melanoma inhibitory activity at the cell rear is supported by KCa3.1 potassium channels

“…It is generally accepted that migrating cells are polarized along their axis of movement and establish an intracellular Ca 2+ gradient with a lower [Ca 2+ ] at the cell npg front [14][15][16]. By mediating salt efflux or influx, followed by osmotic water flow, ion channels and transporters play a pivotal role in regulating cell volume during migration.…”

“…By mediating salt efflux or influx, followed by osmotic water flow, ion channels and transporters play a pivotal role in regulating cell volume during migration. These considerations apply in particular to the KCa3.1 channel, which is activated in migrating cells by increased Ca 2+ [16,37], especially at the cell rear [22]. Since KCa3.1 channel expression was observed in malignant melanoma cells [19], we decided to test for KCa3.1-mediated potassium currents in Mel Im cells and to investigate whether there is a direct association of channel activity and MIA protein secretion.…”

“…In addition to setting the cell volume, intracellular Ca 2+ modulates the turnover of actin filaments; an elevation of Ca 2+ promotes actin depolymerization, whereas a low Ca 2+ concentration favors actin polymerization. The regulation of the cytoskeletal migration machinery is supported by the intracellular gradient of Ca 2+ with the higher concentration at the cell rear [14][15][16]. Another relevant factor for the motility of cells is the Ca 2+ -controlled function of calpains in the release of cell-extracellular matrix contacts [17] at the cell rear.…”

“…By modulating turnover of actin filaments [14][15][16], activation of calpain [17] and recycling of integrins, Ca 2+ coordinates different components of the cellular migration machinery. Another player linking intracellular Ca 2+ ions and cell migration is the calcium-activated potassium channel KCa3.1.…”