Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells.

The Journal of Biological Chemistry
Gaspar Peña-MünzenmayerJames E Melvin

Abstract

Transcellular Cl(-) movement across acinar cells is the rate-limiting step for salivary gland fluid secretion. Basolateral Nkcc1 Na(+)-K(+)-2Cl(-) cotransporters play a critical role in fluid secretion by promoting the intracellular accumulation of Cl(-) above its equilibrium potential. However, salivation is only partially abolished in the absence of Nkcc1 cotransporter activity, suggesting that another Cl(-) uptake pathway concentrates Cl(-) ions in acinar cells. To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl(-)/HCO3 (-) exchangers. We found that salivation stimulated by muscarinic and β-adrenergic receptor agonists was normal in the submandibular glands of Ae2(-/-) mice. In contrast, saliva secretion was reduced by 35% in Ae4(-/-) mice. The decrease in salivation was not related to loss of Na(+)-K(+)-2Cl(-) cotransporter or Na(+)/H(+) exchanger activity in Ae4(-/-) mice but correlated with reduced Cl(-) uptake during β-adrenergic receptor activation of cAMP signaling. Direct measurements of Cl(-)/HCO3 (-) exchanger activity revealed that HCO3 (-)-dependent Cl(-) uptake was reduced in the acinar cells of Ae2(-/-) and Ae4(-/-) mice. Moreover, Cl(-)/HCO3 (-) exchanger activity was nearly ab...Continue Reading

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Citations

Mar 12, 2016·Progress in Neurobiology·Hanshu ZhaoZhongling Zhang
Apr 27, 2016·The Journal of General Physiology·Gaspar Peña-MünzenmayerMarcelo A Catalán
Apr 30, 2017·Pflügers Archiv : European journal of physiology·Salam H IbrahimMichael A Gray
Feb 1, 2018·American Journal of Physiology. Cell Physiology·Mark D Parker
Jan 4, 2019·International Journal of Oral Science·Yuichiro KusudaRyuji Hosokawa
Dec 7, 2017·Bulletin of Mathematical Biology·Elías Vera-SigüenzaJames Sneyd
Nov 30, 2018·Bulletin of Mathematical Biology·Elías Vera-SigüenzaJames Sneyd
Mar 13, 2020·Bulletin of Mathematical Biology·Elías Vera-SigüenzaJames Sneyd
Mar 14, 2018·The Journal of Biological Chemistry·Taro MukaiboJames E Melvin
Feb 18, 2021·Bulletin of Mathematical Biology·James SneydDavid I Yule
Sep 30, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Gaspar Peña-MünzenmayerMarcelo A Catalán

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