Alterations in the extracellular Ca2+ or K+ concentration had significant influences on the motility of B16F10 melanoma cells measured in the absence of exogenous integrins using a conventional Boyden chamber assay. At normal K+ concentrations, motility increased slightly when the concentration of Ca2+ was increased 10-fold. At normal Ca2+ concentrations, motility increased by 290% when the extracellular K+ concentration was reduced 10-fold (from control of 5.4 mM to 0.54 mM), and increased to 250% of control levels when the K+ concentration was increased between 30 and 54 mM, but was relatively uninfluenced at K+ concentrations between 5 and 30 mM. Simultaneous application of low concentrations (20 muM) of GdCl3 completely prevented the effects of low and high K+ on motility. Exposure to Gd3+ or Tb3+ also produced a flattening of the cells and enhanced cell attachment. Although the steady state intracellular Ca2+ concentration was not significantly Influenced by the K+ concentration, the resting permeability to divalent cations, determined from Mn2+ quench rates in fura-loaded cells, was significantly increased by a reduction in the K+ concentration. These results indicate that resting Ca2+ influx is critical to the movement of B16F10 melanoma cells, and demonstrate that lanthanides, which block resting Ca2+ influx pathways, are potent antimotility agents. (C) 2002 Lippincott Williams Wilkins.