A Ca2(+)-activated K+ current in ras-transformed fibroblasts is absent from nontransformed cells.
Biochemical similarities between ras proteins and the GTP-binding proteins and correlation of ras-induced cell transformation with altered transmembrane cation fluxes indicate that ras proteins may act to modulate ion channel activity. To test this idea, whole cell, tight-seal, patch-clamp recording was used to compare macroscopic currents of ras-transformed fibroblasts with currents of their nontransformed counterparts. A prominent calcium-activated, voltage-independent potassium current was observed in 83-100% of cells from three separate fibroblast lines transformed by two different oncogenic ras alleles, whereas the same current was present at much smaller amplitudes in only 0-15% of nontransformed cells. The calcium-activated potassium current is blocked by charybdotoxin and by concentrations of tetraethylammonium above 1 mM, but it is insensitive to apamin. Both normal and ras-transformed cells have another calcium-activated current that is not potassium selective, and, consistent with other studies, normal cells display a voltage-activated calcium conductance. These results suggest that the mechanisms by which ras triggers or maintains cell transformation may involve alterations in the number or activity of certain ion channels, in particular, a type of calcium-activated potassium channel.
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
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D000818:Animals; D001030:Apamin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D018999:Charybdotoxin; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D011905:Genes, ras; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D001030:Apamin; D000001:Calcimycin; D002118:Calcium