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Cancer Research 1981-Jan

Thermosensitivity of the membrane potential of normal and simian virus 40-transformed hamster lymphocytes.

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R B Mikkelsen
B Koch

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The effects of temperature in the fever range (37-42 degrees) on the membrane potentials of normal and simian virus 40-transformed hamster lymphocytes were analyzed. The transmembrane distributions of radiolabeled triphenylmethylphosphonium and thiocyanate were measured, and they provide upper and lower limits for the normal cell membrane potential at 37 degrees of -48 +/- 6 (S.D.) and -31 +/- 5 mV and for the tumor cells, -36 +/- 4 and -19 +/- 2 mV. The mitochondrial contribution to the triphenylmethylphosphonium-measured membrane potential, 5 to 10 mV for both splenocytes and simian virus 40-transformed lymphocytes, was estimated by utilizing antimycin A and carbonylcyanide-m-chlorophenylhydrazone to inhibit generation of a mitochondrial membrane potential. Incubation for 1 to 2 hr at 38-42 degrees resulted in a 6- to 15-mV depolarization of normal cells and a 2- to 6-mV hyperpolarization of tumor cells. Both depolarization and hyperpolarization were fully reversible by subsequent incubation at 37 degrees and insensitive to antimycin A and carbonyl-cyanide-m-chlorophenylhydrazone. The membrane potential of normal splenocytes when measured with triphenylmethylphosphonium at 37 degrees was depolarized by 35% with 1 mM ouabain and thermally induced depolarization was blocked. The membrane potential of tumor cells at 37 degrees was insensitive to ouabain; however, the hyperpolarization at 40 degrees was inhibited. The membrane potential of normal lymphocytes stimulated with phytohemagglutinin was depolarized relative to that of nonstimulated control cells and assumed the thermal response characteristics of tumor cells.

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