Membrane potential changes during mitogenic stimulation of mouse spleen lymphocytes.
By monitoring differences in accumulation of the lipophilic cation [(3)H]tetraphenylphosphonium in media containing low or high potassium concentrations [Lichtshtein, D., Kaback, H. R. & Blume, A. J. (1979) Proc. Natl. Acad. Sci. USA 76, 650-654], the membrane potential of lymphocytes from various sources has been estimated. On the basis of this method, the potential of normal mouse spleen lymphocytes (T and B cells) is -65 +/- 2 mV (mean +/- SEM, interior negative). During the course of mitogenic stimulation by concanavalin A, lipopolysaccharide, or fetal calf serum, the membrane potential of murine spleen lymphocytes changes systematically according to the following pattern: (i) early depolarization lasting 2-3 hr, (ii) repolarization over the next 7 hr, and (iii) a final hyperpolarization phase during the last 24-48 hr. During repolarization and hyperpolarization, moreover, there is a direct correlation between the membrane potential and DNA synthesis, as judged by [(3)H]thymidine incorporation. By using isolated T and B cells, it is observed that concanavalin A depolarizes T cells only, whereas lipopolysaccharide depolarizes B cells only. Thus, both mitogens exhibit the same specificity for depolarization as for mitogenic stimulation. On the basis of these observations, it is suggested that the transition of lymphocytes from a resting state to mitotic activity is initiated by depolarization of the plasma membrane.
D000818:Animals; D001769:Blood; D002454:Cell Differentiation; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds; D013154:Spleen / Q000502:physiology
D006133:Growth Substances; D008070:Lipopolysaccharides; D008934:Mitogens; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D003208:Concanavalin A; C013289:tetraphenylphosphonium