Blockade of Ca²⁺-dependent Cl⁻ current in xenopus oocytes by Cl⁻ channel blockers and antimalarial drugs

Effects of Cl channel blockers and antimalarial drugs on the Ca²’-dependent Cl' current in Xenopus oocytes were studied using a two-microelectrode voltage-clamp technique. Chloride channel blockers, such as stilbene disulfonic acids and carboxylic acids, inhibit the Cl current in oocytes. The calculated half-inhibitory concentrations (IC50) of these blockers on the oocyte Cl current demonstrate an order of potency of 4, 4'-diisothio- cyanatostilbene-2, 2'-disulfonic acid > anthracene-9-carboxylic acid > diphenylamine-2- carboxylic acid > indanyloxyacetic acid. This is different from the potency observed in the outwardly rectifying Cl" channels of epithelial cells. The blocking effect of these Cl" channel blockers on the Ca²^-dependent Cl" current in oocytes was observed to be stronger at positive membrane potentials. In addition, various antimalarial drugs, such as quinine’s derivatives and artesunate, inhibit the Ca²⁺-dependent Cl" current in oocytes. These inhibitory' effects on cytoplasmic membrane Cl" channels may be responsible for the pharmacological action and toxic side effects of these compounds.