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id":"R4411","pred":"amod","subj":"T7144","obj":"T7143"},{"id":"R4412","pred":"det","subj":"T7145","obj":"T7146"},{"id":"R4414","pred":"attr","subj":"T7146","obj":"T7134"},{"id":"R4415","pred":"prep","subj":"T7147","obj":"T7146"},{"id":"R4417","pred":"nmod","subj":"T7148","obj":"T7149"},{"id":"R4418","pred":"pobj","subj":"T7149","obj":"T7147"},{"id":"R4420","pred":"punct","subj":"T7150","obj":"T7148"},{"id":"R4421","pred":"prep","subj":"T7151","obj":"T7146"},{"id":"R4422","pred":"amod","subj":"T7152","obj":"T7153"},{"id":"R4423","pred":"amod","subj":"T7153","obj":"T7154"}],"text":"The observation that endolymphatic and perilymphatic K+ concentrations were normal in Slc26a4-/- mice suggests that stria vascularis was able to secrete K+ in spite of the apparent signs of degeneration. The rate of K+ secretion necessary to maintain endolymphatic K+ concentration, however, may be less than necessary in Slc26a4+/+ mice given the reduced numbers of sensory hair cells, which provide a major pathway for K+ exit from endolymph [30,31]. In order to substantiate the view that stria vascularis in Slc26a4-/- secretes K+, we measured the magnitude of the bumetanide-sensitive current exiting stria vascularis across the apical membrane of strial marginal cells and determined the expression of the proteins KCNQ1, KCNE1 and SLC12A2, which are essential for K+ secretion [20,32,33], and of GJB2 (Cx26), which is thought to contribute to K+ cycling [23]. K+ secretion is known to be sensitive to 10-5 M bumetanide, a loop-diuretic that inhibits the Na+/2Cl-/K+ cotransporter SLC12A2 [26]. Bumetanide-sensitive currents were found in both Slc26a4+/+ and Slc26a4-/- mice although the magnitude of the current was significantly smaller in Slc26a4-/- mice (22 ± 6 μA/cm2, n = 4 versus 14 ± 2 μA/cm2, n = 4). KCNQ1 and KCNE1, subunits of the secretory K+ channel, were co-localized in the apical membrane of strial marginal cells; the Na+/2Cl-/K+ cotransporter SLC12A2, which is located in the basolateral membrane of strial marginal cells, was found in stria vascularis; and the gap junction protein GJB2 was found in spiral ligament of Slc26a4+/+ and Slc26a4-/- mice (Fig. 8). Co-localization of KCNQ1 and KCNE1 proteins was also observed in vestibular dark cells (Fig. 1i). Expression of KCNQ1 protein in stria vascularis of Slc26a4-/- mice is consistent with the finding of KCNQ1 mRNA expression (Fig. 3). These observations make it unlikely that the primary cause of the loss of the endocochlear potential is a compromise of K+ secretion by strial marginal cells or a compromise of gap junction mediated K+ cycling."}

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observation that endolymphatic and perilymphatic K+ concentrations were normal in Slc26a4-/- mice suggests that stria vascularis was able to secrete K+ in spite of the apparent signs of degeneration. The rate of K+ secretion necessary to maintain endolymphatic K+ concentration, however, may be less than necessary in Slc26a4+/+ mice given the reduced numbers of sensory hair cells, which provide a major pathway for K+ exit from endolymph [30,31]. In order to substantiate the view that stria vascularis in Slc26a4-/- secretes K+, we measured the magnitude of the bumetanide-sensitive current exiting stria vascularis across the apical membrane of strial marginal cells and determined the expression of the proteins KCNQ1, KCNE1 and SLC12A2, which are essential for K+ secretion [20,32,33], and of GJB2 (Cx26), which is thought to contribute to K+ cycling [23]. K+ secretion is known to be sensitive to 10-5 M bumetanide, a loop-diuretic that inhibits the Na+/2Cl-/K+ cotransporter SLC12A2 [26]. Bumetanide-sensitive currents were found in both Slc26a4+/+ and Slc26a4-/- mice although the magnitude of the current was significantly smaller in Slc26a4-/- mice (22 ± 6 μA/cm2, n = 4 versus 14 ± 2 μA/cm2, n = 4). KCNQ1 and KCNE1, subunits of the secretory K+ channel, were co-localized in the apical membrane of strial marginal cells; the Na+/2Cl-/K+ cotransporter SLC12A2, which is located in the basolateral membrane of strial marginal cells, was found in stria vascularis; and the gap junction protein GJB2 was found in spiral ligament of Slc26a4+/+ and Slc26a4-/- mice (Fig. 8). Co-localization of KCNQ1 and KCNE1 proteins was also observed in vestibular dark cells (Fig. 1i). Expression of KCNQ1 protein in stria vascularis of Slc26a4-/- mice is consistent with the finding of KCNQ1 mRNA expression (Fig. 3). These observations make it unlikely that the primary cause of the loss of the endocochlear potential is a compromise of K+ secretion by strial marginal cells or a compromise of gap junction mediated K+ cycling."}

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observation that endolymphatic and perilymphatic K+ concentrations were normal in Slc26a4-/- mice suggests that stria vascularis was able to secrete K+ in spite of the apparent signs of degeneration. The rate of K+ secretion necessary to maintain endolymphatic K+ concentration, however, may be less than necessary in Slc26a4+/+ mice given the reduced numbers of sensory hair cells, which provide a major pathway for K+ exit from endolymph [30,31]. In order to substantiate the view that stria vascularis in Slc26a4-/- secretes K+, we measured the magnitude of the bumetanide-sensitive current exiting stria vascularis across the apical membrane of strial marginal cells and determined the expression of the proteins KCNQ1, KCNE1 and SLC12A2, which are essential for K+ secretion [20,32,33], and of GJB2 (Cx26), which is thought to contribute to K+ cycling [23]. K+ secretion is known to be sensitive to 10-5 M bumetanide, a loop-diuretic that inhibits the Na+/2Cl-/K+ cotransporter SLC12A2 [26]. Bumetanide-sensitive currents were found in both Slc26a4+/+ and Slc26a4-/- mice although the magnitude of the current was significantly smaller in Slc26a4-/- mice (22 ± 6 μA/cm2, n = 4 versus 14 ± 2 μA/cm2, n = 4). KCNQ1 and KCNE1, subunits of the secretory K+ channel, were co-localized in the apical membrane of strial marginal cells; the Na+/2Cl-/K+ cotransporter SLC12A2, which is located in the basolateral membrane of strial marginal cells, was found in stria vascularis; and the gap junction protein GJB2 was found in spiral ligament of Slc26a4+/+ and Slc26a4-/- mice (Fig. 8). Co-localization of KCNQ1 and KCNE1 proteins was also observed in vestibular dark cells (Fig. 1i). Expression of KCNQ1 protein in stria vascularis of Slc26a4-/- mice is consistent with the finding of KCNQ1 mRNA expression (Fig. 3). These observations make it unlikely that the primary cause of the loss of the endocochlear potential is a compromise of K+ secretion by strial marginal cells or a compromise of gap junction mediated K+ cycling."}

{"project":"2_test","denotations":[{"id":"15320950-2778743-12070982","span":{"begin":445,"end":447},"obj":"2778743"},{"id":"15320950-2393707-12070983","span":{"begin":448,"end":450},"obj":"2393707"},{"id":"15320950-8982171-12070984","span":{"begin":785,"end":787},"obj":"8982171"},{"id":"15320950-11226272-12070985","span":{"begin":788,"end":790},"obj":"11226272"},{"id":"15320950-10401008-12070986","span":{"begin":791,"end":793},"obj":"10401008"},{"id":"15320950-12031509-12070987","span":{"begin":862,"end":864},"obj":"12031509"},{"id":"15320950-7642451-12070988","span":{"begin":996,"end":998},"obj":"7642451"}],"text":"The observation that endolymphatic and perilymphatic K+ concentrations were normal in Slc26a4-/- mice suggests that stria vascularis was able to secrete K+ in spite of the apparent signs of degeneration. The rate of K+ secretion necessary to maintain endolymphatic K+ concentration, however, may be less than necessary in Slc26a4+/+ mice given the reduced numbers of sensory hair cells, which provide a major pathway for K+ exit from endolymph [30,31]. In order to substantiate the view that stria vascularis in Slc26a4-/- secretes K+, we measured the magnitude of the bumetanide-sensitive current exiting stria vascularis across the apical membrane of strial marginal cells and determined the expression of the proteins KCNQ1, KCNE1 and SLC12A2, which are essential for K+ secretion [20,32,33], and of GJB2 (Cx26), which is thought to contribute to K+ cycling [23]. K+ secretion is known to be sensitive to 10-5 M bumetanide, a loop-diuretic that inhibits the Na+/2Cl-/K+ cotransporter SLC12A2 [26]. Bumetanide-sensitive currents were found in both Slc26a4+/+ and Slc26a4-/- mice although the magnitude of the current was significantly smaller in Slc26a4-/- mice (22 ± 6 μA/cm2, n = 4 versus 14 ± 2 μA/cm2, n = 4). KCNQ1 and KCNE1, subunits of the secretory K+ channel, were co-localized in the apical membrane of strial marginal cells; the Na+/2Cl-/K+ cotransporter SLC12A2, which is located in the basolateral membrane of strial marginal cells, was found in stria vascularis; and the gap junction protein GJB2 was found in spiral ligament of Slc26a4+/+ and Slc26a4-/- mice (Fig. 8). Co-localization of KCNQ1 and KCNE1 proteins was also observed in vestibular dark cells (Fig. 1i). Expression of KCNQ1 protein in stria vascularis of Slc26a4-/- mice is consistent with the finding of KCNQ1 mRNA expression (Fig. 3). These observations make it unlikely that the primary cause of the loss of the endocochlear potential is a compromise of K+ secretion by strial marginal cells or a compromise of gap junction mediated K+ cycling."}