K+ efflux in NIH mouse 3T3 cells and transformed derivatives: dependence on extracellular Ca2+ and phorbol esters.
In culture medium deficient in Ca2+, NIH mouse 3T3 cells lose K+, gain Na+, and stop growing. A marked increase in the rate of K+ efflux accounts for this loss; Na+, K+-ATPase pump activity increases but does not fully compensate for enhanced K+ efflux. Phorbol esters and cycloheximide inhibit K+ loss in Ca2+-deficient medium. Phorbol esters inhibit K+ efflux from human fibroblasts as well, even at physiological levels of Ca2+. Two cell lines derived from NIH-3T3, one transformed by a simian virus 40 deletion mutant, the other by the polyoma virus oncogene encoding the middle-sized tumor antigen, retain K+ and can multiply in medium with low Ca2+. Efflux of K+ from these cells is relatively insensitive to reduced Ca2+ concentration, phorbol esters, and cycloheximide. The results suggest the following hypothesis: a channel, nonselective for K+ and Na+, opens when NIH-3T3 cells are in Ca2+-deficient medium; the channel is controlled by the receptor for phorbol ester (protein kinase C) and may also be regulated by a short-lived protein.
Lubin
M
M
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755.
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002413:Cations, Divalent; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D003513:Cycloheximide / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D010703:Phorbol Esters / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D012414:Rubidium Radioisotopes / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002413:Cations, Divalent; D010703:Phorbol Esters; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D003513:Cycloheximide; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium