Potassium channels and regulation of proliferation of human melanoma cells.

Abstract

1. Ion channels and their possible relation to cell proliferation have been studied in a human melanoma cell line (IGR 1). Membrane currents were recorded by the patch-clamp technique using the cell-attached, cell-free and whole-cell mode. Cell growth was monitored by counting the number of cells at different days after seeding and [3H]thymidine incorporation. 2. A voltage-dependent 10 pS non-inactivating potassium channel (delayed rectifier) is the most commonly observed ion channel in this type of human cell. The channel is active at the normal resting potential and can be blocked by tetraethylammonium chloride (TEA) and also by a membrane-permeable cyclic adenosine monophosphate (8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, cyclic AMP). A second type of potassium channel shows properties similar to voltage-dependent A-type potassium channels with complete inactivation. 3. A voltage-independent, non-selective cation channel with a single-channel conductance of approximately 20 pS could be seen in only 8% of the patches. Its properties of modulation are still unknown. 4. The incidence of the 10 pS, non-inactivated potassium channel was maximal at the fourth day after seeding (in 89% of the patches) and was significantly reduced at the seventh day (in 35% of the patches). 5. [3H]thymidine incorporation is maximal at the third day after seeding and is reduced when cells are grown in the presence of TEA or cyclic AMP. This peak of maximal [3H]thymidine incorporation correlated with the incidence of non-inactivated potassium channels. 6. In the presence of TEA or cyclic AMP, growth of the cells is inhibited. We suppose that due to block of potassium channels, most of the melanoma cells are not able to enter the S-phase in the cell division cycle. 7. It is concluded that delayed rectifier potassium channels are involved in the control of melanoma cell proliferation. A similar finding has been reported for K+ channels in T-lymphocytes and human breast carcinoma cells. It is suggested that potassium channels may be involved in controlling the driving force for a calcium influx thereby interacting with Ca(2+)-dependent cell cycle control proteins.

Oncogenic potential of TASK3 (Kcnk9) depends on K+channel function

“…Inhibition of K ϩ channels by pharmacological agents has been found to inhibit cell proliferation in normal human lymphocytes (18)(19)(20)(21), human melanoma cells (22,23), small cell lung cancer (24), breast (25), and prostate (26) cancer cells. The role of K ϩ channels in cellular proliferation has been thought to be indirect, by either the possible influence of K ϩ channels on the intracellular Ca 2ϩ concentration (27) or, alternatively, the control of cell volume via K ϩ channels (28).…”

Re-expression of Detachment-inducible Chloride Channel mCLCA5 Suppresses Growth of Metastatic Breast Cancer Cells

“…proliferation of multiple cell types, including normal lymphocytes, melanoma, breast and prostate cancer cell lines, and glial cells (43)(44)(45)(46)(47). Concordantly, some K ϩ channels are upregulated during tumorigenesis and are pro-oncogenic.…”

Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

“…Ion channels, including K þ channels, are important for cell cycle and cell proliferation and are found in a variety of cancer cells (Nilius and Wohlrab, 1992;Skryma et al, 1997;Ouadid-Ahidouch et al, 2000;Fraser et al, 2003;Parihar et al, 2003;Farias et al, 2004;Jager et al, 2004). It has been shown that K þ channels play a role in controlling proliferation and transformation of epithelial cells (Pardo et al, 1999).…”