As for KCC, substantial inhibition (about 80%) was observed without pre-treatment (Fig. 2). In these experiments and similar to findings shown in Fig. 1, following complete deoxygenation sicklingwas unaffected by the presence of o-vanillin (being 98±4%,mean± S.E.M., n=5, of control values in the absence of o-vanillin). It would therefore appear that o-vanillin can substantially inhibit both KCC and the Gardos channel without any inhibition of HbS polymerisation and sickling. Similar findingswere obtained using RBCs fromthe secondmain genotype of SCD patients, heterozygous HbSC individuals, with KCC and Gardos channel activities reduced to b20% their magnitude in the absence of o-vanillin (5 mM).