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      K(+) channel-dependent migration of fibroblasts and human melanoma cells.

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          Abstract

          Previously, we showed that migration of transformed renal epithelial cells (MDCK-F cells) is a K(+) channel-dependent process [J Clin Invest 1994;93:1631]. In order to determine whether K(+) channel activity is a general requirement for locomotion, we extended our observations to NIH3T3 fibroblasts and human melanoma cells. Migration of both cell types and its dependence on K(+) channel activity was measured at the single cell level by time lapse photography in the absence and presence of the specific K(+) channel blocker charybdotoxin (CTX). Locomotion of both cell types is inhibited by K(+) channel blockade. CTX slows down migration of fibroblasts and of melanoma cells dose-dependently by up to 61 +/- 11%. These findings suggest that K(+) channel activity is a general prerequisite for migration. To determine whether CTX-induced inhibition of migration of fibroblasts and melanoma cells involves quantitative changes of actin filaments, we indirectly measured filamentous actin by quantitating binding of fluorescently labeled phalloidin. Whereas CTX elicits a decrease of bound phalloidin in fibroblasts there is an increase in melanoma cells. Since migration of tumor cells is required for invading surrounding tissue, we developed an assay to test whether CTX-induced inhibition of migration also impairs invasion of melanoma cells. Melanoma cells were seeded on a layer of high resistance renal epithelial cells (MDCK cells clone C7; transepithelial resistance R(te) >3,000 Omegacm(2)) and R(te) was measured daily. R(te) starts to decrease 2 days after seeding of melanoma cells onto MDCK-C7 cells. By day 7, R(te) has dropped to 24 +/- 1.5% of control. K(+) channel blockade with CTX (10 nmol/l) cannot prevent or delay this drop of R(te). R(te) reaches the same level with or without CTX. These results indicate that the disruption of an epithelial layer, unlike migration of melanoma cells, cannot be modulated by K(+) channel blockade.

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          Author and article information

          Journal
          Cell Physiol Biochem
          Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
          S. Karger AG
          1015-8987
          1015-8987
          1999
          : 9
          : 3
          Affiliations
          [1 ] Physiologische Institute, Würzburg, Deutschland. albrecht.schwab@mail.uni-wuerzberg.de
          Article
          16309
          10.1159/000016309
          10494026
          110cb1aa-9c8f-4ba9-9f64-d327203cdf40
          History

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