Functional and molecular characterization of the fluid secretion mechanism in human parotid acinar cells
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The strategies available for treating salivary gland hypofunction are limited because relatively little is known about the secretion process in humans. An initial microarray screen detected ion transport proteins generally accepted to be critically involved in salivation. We tested for the activity of some of these proteins, as well as for specific cell properties required to support fluid secretion. The resting membrane potential of human acinar cells was near -51 mV, while the intracellular [Cl-] was ∼62 mM, about fourfold higher than expected if Cl ions were passively distributed. Active Cl- uptake mechanisms included a bumetanide-sensitive Na %2b-K%2b-2Cl- cotransporter and paired DIDS-sensitive Cl-/HCO3- and EIPA-sensitive Na%2b/H%2b exchangers that correlated with expression of NKCC1, AE2, and NHE1 transcripts, respectively. Intracellular Ca2%2b stimulated a niflumic acid-sensitive Cl- current with properties similar to the Ca2%2b-gated Cl channel BEST2. In addition, intracellular Ca2%2b stimulated a paxilline-sensitive and voltage-dependent, large-conductance K channel and a clotrimazolesensitive, intermediate-conductance K channel, consistent with the detection of transcripts for KCNMA1 and KCNN4, respectively. Our results demonstrate that the ion transport mechanisms in human parotid glands are equivalent to those in the mouse, confirming that animal models provide valuable systems for testing therapies to prevent salivary gland dysfunction. Copyright © 2007 the American Physiological Society.
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Channels; Cotransporters; Exchangers; Fluid; Salivary glands; Secretion 4,4' diisothiocyanatostilbene 2,2' disulfonic acid; [5 (n ethyl n isopropyl)amiloride]; [6 methoxy n (3 sulfopropyl)quinolinium]; amiloride derivative; bumetanide; calcium; chloride; chloride channel; clotrimazole; gene product; niflumic acid; paxilline; potassium; potassium intermediate small conductance calcium activated channel subfamily n member 4; potassium large conductance calcium activated channel subfamily m alpha member 1; quinoline derivative; sodium; sodium potassium chloride cotransporter; sodium proton exchange protein; sodium proton exchange protein 1; unclassified drug; voltage gated potassium channel; acinar cell; adult; aged; animal tissue; anion exchange; article; calcium cell level; cell membrane conductance; cell membrane potential; cell secretion; controlled study; drug mechanism; female; gene expression; genetic transcription; human; human tissue; intracellular fluid; ion transport; liquid; male; molecular biology; mouse; nonhuman; nucleotide sequence; parotid gland; priority journal; Adult; Aged; Animals; Body Fluids; Female; Humans; Ion Channels; Male; Middle Aged; Parotid Gland; Water-Electrolyte Balance
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