Signal pathway of mitogen-induced Ca2+-activated K+ currents in young and aged T-cell clones of C57BL/6 mice.
Signal transduction pathways of mitogenic plant lectin, concanavalin A (Con A)- and ionomycin (INM)-induced (Ca2+-dependent K+ currents (I(Con A) and I(INM)) have been compared in young and aged T-cell clones by using the nystatin perforated patch-clamp whole-cell recording technique. In young T-cell clones, Con A evoked a long-lasting outward current which is mediated by the activation of the Ca2+-dependent K+ channels. The Ca2+ ionophore, INM, evoked a short-lasting Ca2+-dependent outward K+ current (I(INM)). The protein tyrosine kinase (PTK) inhibitor, herbimycin A (3 x 10(-6) M), but not the G protein blocker, pertussis toxin (PTX, 500 ng ml(-1)), completely prevented the I(Con A), but did not affect the I(INM). In aged T-cell clones, Con A fails to evoke any current response, while INM evokes an outward current which is comparable to that in a young T-cell clone. It is concluded that PTK, but not PTX-sensitive G proteins, plays a critical role in mediation of the signal transduction from Con A stimulation to activation of the Ca2+-dependent K+ channels, and that an impairment of the early signal pathway, perhaps the PTK, might be involved in the mechanism of the age-related decline of the proliferative response of T-lymphocytes to mitogenic stimulation.
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan. jiewubni@yahoo.com
J
J
Wu
Y X
YX
Zeng
K
K
Hirokawa
D000818:Animals; D020013:Calcium Signaling; D016922:Cellular Senescence / Q000502:physiology*; D003208:Concanavalin A / Q000378:metabolism / Q000494:pharmacology; D007424:Intracellular Fluid; D015759:Ionomycin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D008934:Mitogens; D015221:Potassium Channels; D003208:Concanavalin A; D015759:Ionomycin