Mitogen-induced changes in Ca2+ permeability are not mediated by voltage-gated K+ channels.
Binding of mitogenic lectins to T lymphocytes results in elevated cytoplasmic Ca2+ concentrations ([Ca2+]i). This change in [Ca2+]i is thought to be essential for cellular proliferation. In addition, the lectins increase the conductance to K+ through voltage-sensitive channels. Based on the inhibitory effect of K+ channel blockers on lectin-induced mitogenesis, it has been suggested that Ca2+ could enter the cells through these activated K+ channels (Chandy, K. G., De Coursey, T. E., Cahalan, M. D., McLaughlin, C., and Gupta, S. (1984) J. Exp. Med. 160, 369-385; Chandy, K. G., De Coursey, T. E., Cahalan, M. D., and Gupta, S. (1985) J. Clin. Immunol. 5, 1-5). This hypothesis was tested experimentally by measuring the effect of activation or blockade of K+ channels on [Ca2+]i using quin-2 and indo-1 and by determining the effect of K+ channel blockers on lectin-induced proliferation. We found that: depolarization of the membrane, which is expected to open the K+ channels, failed to increase [Ca2+]i, K+ channel blockers such as tetraethylammonium and 4-aminopyridine had only a marginal effect on the lectin-induced increase in [Ca2+]i, and the inhibitory effect of K+ channel blockers on proliferation was found to be nonspecific, occurring also when proliferation was triggered by phorbol esters under conditions where [Ca2+]i is not elevated. It is concluded that the lectin-induced changes in [Ca2+]i are not mediated by the opening of voltage-gated K+ channels.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials; D008934:Mitogens / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011803:Quinine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D007473:Ion Channels; D008934:Mitogens; D010835:Phytohemagglutinins; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D011803:Quinine; D015761:4-Aminopyridine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium