{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T05:18:31Z","timestamp":1785561511835,"version":"3.56.0"},"reference-count":46,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Stein Innovation Award"],"award-info":[{"award-number":["Stein Innovation Award"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["EY007003"],"award-info":[{"award-number":["EY007003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:p> Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing &gt;70% of the eye\u2019s refractive power. However, for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye. In freshly excised rat conjunctiva, perforated-patch recordings demonstrated that a \u226510% rise in osmolarity triggers goblet cells to rapidly generate a ~15-mV hyperpolarization due to the oxidant-dependent activation of ATP-sensitive K<jats:sup>+<\/jats:sup> (K<jats:sub>ATP<\/jats:sub>) channels. High-resolution membrane capacitance measurements used to monitor exocytosis revealed that this hyperpolarization results in an approximately fourfold boost in exocytotic activity evoked by cholinergic input, which in vivo occurs via a neural reflex and depends chiefly on calcium influxing down its electro-gradient. We discovered that this adaptive response is transient. During 30\u201380 min of hyperosmolarity, development of a depolarizing nonspecific cation conductance fully counterbalances the K<jats:sub>ATP<\/jats:sub>-driven hyperpolarization and thereby eliminates the exocytotic boost. We conclude that hyperosmotic-induced hyperpolarization is a previously unappreciated mechanism by which goblet cells respond to transient ocular dryness. Loss of this voltage increase during long-term dryness\/hyperosmolarity may account for the clinical conundrum that goblet cells in chronically dry eyes can remain filled with mucin even though the tear film is hyperosmotic and mucin-deficient. <\/jats:p>","DOI":"10.1152\/ajpcell.00077.2018","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T21:03:38Z","timestamp":1524085418000},"page":"C236-C246","source":"Crossref","is-referenced-by-count":17,"title":["Role of ion channels in the functional response of conjunctival goblet cells to dry eye"],"prefix":"10.1152","volume":"315","author":[{"given":"Donald G.","family":"Puro","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences and Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 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