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Expression of BK channels and Na + -K + pumps in the apical membrane of lacrimal acinar cells suggests a new molecular mechanism for primary tear-secretion.

Ocular Surface 2019 January 25
PURPOSE: Primary fluid secretion in secretory epithelia relies on the unidirectional transport of ions and water across a single cell layer. This mechanism requires the asymmetric apico-basal distribution of ion transporters and intracellular Ca2+ signaling. The primary aim of the present study was to verify the localization and the identity of Ca2+ -dependent ion channels in acinar cells of the mouse lacrimal gland.

METHODS: Whole-cell patch-clamp-electrophysiology, spatially localized flash-photolysis of Ca2+ and temporally resolved digital Ca2+ -imaging was combined. Immunostaining of enzymatically isolated mouse lacrimal acinar cells was performed.

RESULTS: We show that the Ca2+ -dependent K+ -conductance is paxilline-sensitive, abundant in the luminal, but negligible in the basal membrane; and co-localizes with Cl- -conductance. These data suggest that both Cl- and K+ are secreted into the lumen and thus they account for the high luminal [Cl- ] (∼141 mM), but not for the relatively low [K+ ] (<17 mM) of the primary fluid. Accordingly, these results also imply that K+ must be reabsorbed from the primary tear fluid by the acinar cells. We hypothesized that apically-localized Na+ -K+ pumps are responsible for K+ -reabsorption. To test this possibility, immunostaining of lacrimal acinar cells was performed using anti-Na+ -K+ ATP-ase antibody. We found positive fluorescence signal not only in the basal, but in the apical membrane of acinar cells too.

CONCLUSIONS: Based on these results we propose a new primary fluid-secretion model in the lacrimal gland, in which the paracellular pathway of Na+ secretion is supplemented by a transcellular pathway driven by apical Na+ -K+ pumps.

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