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  • Title: Bumetanide-induced enlargement of the intercellular space in the stria vascularis critically depends on Na+ transport.
    Author: Higashiyama K, Takeuchi S, Azuma H, Sawada S, Yamakawa K, Kakigi A, Takeda T.
    Journal: Hear Res; 2003 Dec; 186(1-2):1-9. PubMed ID: 14644454.
    Abstract:
    The intercellular space in the stria vascularis (intrastrial space) is a closed space and isolated from both the endolymph and the perilymph in normal tissue. Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space in association with a decline in the endocochlear potential. It is known that bumetanide inhibits the Na+-K+-2Cl- cotransporter, which is expressed abundantly in the basolateral membrane of marginal cells. We studied ionic mechanisms underlying the bumetanide-induced enlargement of the intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with artificial perilymph containing 100 microM bumetanide caused marked enlargement of the intrastrial space, as reported previously. Removal of K+ from the perilymph did not affect the bumetanide-induced enlargement, whereas removal of Na+ from the perilymph inhibited it almost completely. Perilymph containing 1 mM amiloride also inhibited the enlargement of the intrastrial space almost completely. These results indicate that perilymphatic Na+, but not K+, and amiloride-sensitive pathways are essential to the bumetanide-induced enlargement of the intrastrial space. Two possible pathways could yield these results. Na+ in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane; Na+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na+-K+-ATPase in the basolateral membrane of them. Another, less likely possibility is that Na+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na+-K+-ATPase of intermediate cells.
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