Clotrimazole and efaroxan inhibit red cell Gardos channel independently of imidazoline I-1 and I-2 binding sites

In the present report, we investigated the potential involvement of imidazoline I-1 and I-2 binding sites in the inhibition of the Ca2+-activated K+ channel (Gardos channel) by clotrimazole in human red cells. Ca2+-activated Rb-86 influx was inhibited by clotrimazole and efaroxan but not by the imidazoline binding site ligands clonidine, moxonidine, cirazoline and idazoxan (100 mu M). Binding studies with [H-3]idazoxan and [H-3]p-aminoclonidine did not reveal the expression of I-1 and I-2 binding sites in erythrocytes. These data indicate that the effects of clotrimazole and efaroxan on the erythrocyte Ca2+-activated K+ channel may be mediated by a 'non-I-1/non-I-2' binding site.