Increased voltage-gated potassium conductance during interleukin 2-stimulated proliferation of a mouse helper T lymphocyte clone.
Recent work has demonstrated the presence of voltage-gated potassium channels in human peripheral blood T lymphocytes (Matteson, R., and C. Deutsch, 1984, Nature (Lond.), 307:468-471; DeCoursey T. E., T. G. Chandy, S. Gupta, and M. D. Cahalan, 1984, Nature (Lond.), 307:465-468) and a murine cytolytic T-cell clone (Fukushima, Y., S. Hagiwara, and M. Henkart, 1984, J. Physiol., 351:645-656). Using the whole cell patch clamp, we have found a potassium conductance with similar properties in a murine noncytolytic T lymphocyte clone, L2. Under voltage clamp, a step from a holding potential of -70 mV to +50 mV produces an average outward current of 100-150 pA in "quiescent" L2 cells at the end of their weekly maintenance cycle. When these cells are stimulated with human recombinant interleukin 2 (rIL2, 100 U/ml), they grow in size and initiate DNA synthesis at approximately 24 h. Potassium conductance is increased as early as 8 h after stimulation with rIL2 and rises to a level 3-4 times that of excipient controls by 24 h. The level remains elevated through 72 h, but as the cells begin to leave the cell cycle at 72-96 h, the conductance decreases quickly to a value only slightly higher than the initial one. Quinine, a blocker of this conductance, markedly reduces the rate at which L2 cells traverse the cell cycle, while also reducing the rate of stimulated protein synthesis. The regulation of potassium conductance in L2 cells during rIL2-stimulated proliferation suggests that potassium channel function may play a role in support of the proliferative response.
Lee
S C
SC
Sabath
D E
DE
Deutsch
C
C
Prystowsky
M B
MB
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003513:Cycloheximide / Q000494:pharmacology; D004553:Electric Conductivity; D007376:Interleukin-2 / Q000276:immunology*; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D051379:Mice; D011188:Potassium / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011803:Quinine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*
D007376:Interleukin-2; D007473:Ion Channels; D003513:Cycloheximide; D011803:Quinine; D011188:Potassium