Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin and cetiedil

Abstract

Quinidine and Ba 2+, non-selective K +-channel blockers, have previously been shown to inhibit antigen-induced mediator (β-hexosaminidase) release from RBL-2H3 cells, a mucosal-type mast cell line. We therefore used selective blockers of Ca 2+-activated and other K + channels to determine if there was a role for these channels in antigen-induced mediator release. Charybdotoxin and cetiedil dose-dependently inhibited β-hexosaminidase release with IC 50 values of 133 nM and 84 μM, respectively. Charybdotoxin also inhibited the repolarization phase of the antigen-induced biphasic change in the membrane potential (IC 50 84 nM), antigen-stimulated 86Rb +-efflux and increase in free intracellular calcium, [Ca 2+] i. Iberiotoxin, margatoxin, apamin and tetraethylammonium had no effect on β-hexosaminidase release. These results suggest that K + conductances play a significant role in mediator release from RBL-2H3, that these conductances are of the intermediate conductance Ca 2+-activated K + channel (IK Ca) type, and that they are somewhat similar to those which have been described in red blood cells, though they are much less sensitive to clotrimazole.