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

Gaspar Peña-Münzenmayer1, Marcelo A Catalán1, Yusuke Kondo2

  • 1From the Secretory Mechanisms and Dysfunction Section, Division of Intramural Research, NIDCR, National Institutes of Health, Bethesda, Maryland 20892.

The Journal of Biological Chemistry
|March 7, 2015
PubMed

Insights

The study found that Ae4 anion exchangers are crucial for salivary gland fluid secretion by facilitating chloride uptake, particularly during beta-adrenergic stimulation. This highlights a key mechanism beyond Nkcc1 for regulating salivation.

Area of Science:

  • Physiology
  • Molecular Biology
  • Cellular Biology

Background:

  • Transcellular chloride movement is essential for salivary gland fluid secretion.
  • Basolateral Na(+)-K(+)-2Cl(-) cotransporters (Nkcc1) are critical for intracellular chloride accumulation.
  • Partial salivation reduction without Nkcc1 suggests alternative chloride uptake pathways.

Purpose of the Study:

  • To investigate the role of Cl(-)/HCO3(-) exchangers, specifically Ae2 and Ae4, in salivary gland fluid secretion.
  • To identify alternative molecular mechanisms for chloride uptake in acinar cells.

Main Methods:

  • Studied mice lacking functional Ae2 and Ae4 Cl(-)/HCO3(-) exchangers (Ae2(-/-), Ae4(-/-), and double knock-out).
  • Measured saliva secretion stimulated by muscarinic and β-adrenergic receptor agonists.
  • Assessed Cl(-) uptake and Cl(-)/HCO3(-) exchanger activity in acinar cells.

Main Results:

  • Salivation was normal in Ae2(-/-) mice but reduced by 35% in Ae4(-/-) mice.
  • Reduced salivation in Ae4(-/-) mice correlated with decreased Cl(-) uptake during β-adrenergic stimulation.
  • Cl(-)/HCO3(-) exchanger activity was diminished in Ae2(-/-) and Ae4(-/-) mice, and nearly abolished in double knock-outs.

Conclusions:

  • Both Ae2 and Ae4 anion exchangers are functionally expressed in submandibular acinar cells.
  • Ae4 expression is critical for the cAMP-dependent regulation of salivary fluid secretion.
  • Ae4 represents a significant alternative pathway for chloride uptake influencing salivation.

Keywords:
BicarbonateChloride TransportEpitheliumExchangerSalivary GlandSecretion

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