Blockade of Ca2+-Dependent Cl– Current in Xenopus Oocytes by C– Channel Blockers and Antimalarial Drugs

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Abstract
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’-diisothiocyanatostilbene-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.

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