Stimulation of K+ flux into mitochondria by phenylarsine oxide

The dithiol-reactive reagent phenylarsine oxide causes a pH-dependent stimulation of unidirectional K⁺ flux into respiring rat liver mitochondria. This stimulation is diminished by subsequent addition of either the dithiol 2,3-dimercaptopropanol or the monothiol 2-mercaptoethanol. In contrast, uncoupling by phenylarsine oxide is reversed by 2,3-dimercaptopropanol but not by 2-mercaptoethanol. The data suggest separate sites of interaction of phenylarsine oxide with mechanisms of K⁺ entry and ATP synthesis. Stimulatory effects of mersalyl and phenylarsine oxide on K⁺ influx are not additive. Thus PheASO and mersalyl may affect K⁺ influx at a common site. Pretreatment of the mitochondria with DCCD, which inhibits K⁺ influx, fails to alter sensitivity to PheAsO or mersalyl. Thus the DCCD binding site associated with the K⁺ influx mechanism appears to be separate from and independent of the sulfhydryl group(s) which mediate stimulation of K⁺ influx by PheAsO and mersalyl.PheAsO, like mersalyl, also increases the rate of unidirectional K⁺ efflux from respiring mitochondria. The combined presence of PheAsO plus mersalyl causes a greater stimulation of K⁺ efflux than is observed with either reagent alone.Abbreviations used: BAL, British AntilLewisite or 2,3-dimercaptopropanol; DCCD, dicyclohexylcarbodiimide; DBCT, dibutylchloromethyltin chloride; 2-ME, 2-mercaptoethanol; PheAsO, phenylarsine oxide.