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It is conceivable that loss of pendrin, which may secrete HCO3 - into endolymph, results in an accumulation of HCO3 - and an alkalinization of the intrastrial spaces. This extracellular alkalinization may enhance free radical stress, since it may inhibit the uptake of cysteine and thereby limit production of the protective glutathione [38]. Support for the hypothesis of enhanced free radical stress comes from the observed hyperpigmentation in mice lacking pendrin. Strial hyperpigmentation has also been observed in other conditions that are associated with free radical stress, such as acoustic trauma [37]. Alterations in the cytosolic pH in conjunction with free radical stress may lead to the loss of KCNJ10 protein expression in strial intermediate cells. Function and expression of other K+ channels has been shown to be controlled by the cytosolic pH and free radicals, which encode the metabolic state of the cell [39]. Suppression of the KCNJ10 K+ channel in strial intermediate cells, which is essential for the generation of the endocochlear potential, is probably the direct cause of deafness in Slc26a4-/- mice and patients suffering from Pendred 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