We demonstrate that blockade of the lymphocyte voltage-gated K+ channel by charybdotoxin (CTX) inhibits lymphocyte mitogenesis. Charybdotoxin blocks conductance with a Ki of 0.3 nM and inhibits mitogen- and antigen-stimulated proliferation with a Ki of 0.5 nM. As opposed to the other blockers of the lymphocyte K+ channel, the inhibition of mitogenesis by CTX can be overcome selectively by exogenous recombinant interleukin 2 (IL-2); endogenous levels of IL-2 in the culture supernatants of stimulated cells are decreased by the presence of CTX. Our results suggest that the voltage-gated K+ channel is either directly or indirectly involved in IL-2 synthesis and/or secretion.
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