Salt-inducible kinase 1 is present in lung alveolar epithelial cells and regulates active sodium transport

Because the pulmonary alveolar epithelium separates air spaces from a fluid-filled compartment, it is expected that this barrier would be highly resistant to the flow of solutes and water. Investigation of alveolar epithelial resistance has been limited due to the complex anatomy of adult mammalian lung. Previous efforts to study isolated alveolar epithelium cultured on porous substrata yielded leaky monolayers. In this study, alveolar epithelial cells isolated from rat lungs and grown on tissue culture-treated Nucleopore filters resulted in tight monolayers with transepithelial resistance greater than 2,000 omega.cm2. Changes in bioelectric properties of these alveolar epithelial monolayers in response to ouabain, amiloride, and terbutaline are consistent with active sodium transport across a polarized barrier. 22Na flux measurements under short-circuit conditions directly confirm net transepithelial absorption of sodium by alveolar epithelial cells in the apical to basolateral direction, comparable to the observed short-circuit current (4.37 microA/cm2). The transport properties of these tight monolayers may be representative of the characteristics of the mammalian alveolar epithelial barrier in vivo.

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Effects of EGF on alveolar epithelial junctional permeability and active sodium transport

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1996.270.4.l559 ◽

1996 ◽

Vol 270 (4) ◽

pp. L559-L565 ◽

Cited By ~ 18

Author(s):

Z. Borok ◽

A. Hami ◽

S. I. Danto ◽

R. L. Lubman ◽

K. J. Kim ◽

...

Keyword(s):

Sodium Transport ◽

Egf Receptor ◽

Alveolar Epithelial Cell ◽

Short Circuit ◽

Specific Inhibitor ◽

Egf Receptors ◽

Active Sodium ◽

Alveolar Epithelial ◽

Active Sodium Transport ◽

Junctional Permeability

We evaluated the effects of epidermal growth factor (EGF) on transepithelial resistance (Rt) and active ion transport by alveolar epithelial cell (AEC) monolayers on tissue culture-treated polycarbonate filters. Rat type II cells were cultured in completely defined serum-free medium (MDSF) or MDSF supplemented with EGF. The addition of EGF from either day 0 (chronic) or day 4 (subacute) resulted in significant increases in Rt and short-circuit current (ISC) on day 5. After subacute exposure, these effects were delayed in onset by 6-12 h and sustained for > 24 h. Basolateral (but not apical) EGF was responsible for these effects, which were prevented by preincubation with tyrphostin RG-50864, a reversible specific inhibitor of the EGF receptor tyrosine kinase. ISC decreased, with a sensitivity to apical inhibitors of sodium transport in the order benzamil > amiloride > 5-(N-ethyl-N-isopropyl) amiloride in MDSF +/- EGF, and was completely inhibited by the addition of basolateral ouabain. Net sodium flux and Na+, K+ -ATPase activity both increased approximately 50% in the presence of EGF. These results indicate that 1) EGF decreases tight junctional permeability and increases active sodium transport by AEC monolayers via basolaterally located EGF receptors, and 2) the pathways for AEC sodium entry and exit (+/- EGF) are apical high amiloride affinity sodium channels and basolateral sodium pumps.

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THE EFFECT OF CALCIUM WITHDRAWAL ON THE STRUCTURE AND FUNCTION OF THE TOAD BLADDER

The Journal of Cell Biology ◽

10.1083/jcb.25.3.195 ◽

1965 ◽

Vol 25 (3) ◽

pp. 195-209 ◽

Cited By ~ 63

Author(s):

Richard M. Hays ◽

Bayla Singer ◽

Sasha Malamed

Keyword(s):

Epithelial Cells ◽

Sodium Transport ◽

Short Circuit ◽

Short Circuit Current ◽

Structure And Function ◽

Toad Bladder ◽

Active Sodium ◽

Bathing Medium ◽

Active Sodium Transport ◽

And Function

Previous reports have indicated that calcium is necessary to support active sodium transport by the toad bladder, and may be required as well in the action of vasopressin on both toad bladder and frog skin. The structure and function of the toad bladder has been studied in the absence of calcium, and a reinterpretation of the previous findings now appears possible. When calcium is withdrawn from the bathing medium, epithelial cells detach from one another and eventually from their supporting tissue. The short-circuit current (the conventional means of determining active sodium transport) falls to zero, and vasopressin fails to exert its usual effect on short-circuit current and water permeability. However, employing an indirect method for the estimation of sodium transport (oxygen consumption), it is possible to show that vasopressin exerts its usual effect on Qoo2 when sodium is present in the bathing medium. Hence, it appears that the epithelial cells maintain active sodium transport when calcium is rigorously excluded from the bathing medium, and continue to respond to vasopressin. The failure of conventional techniques to show this can be attributed to the structural alterations in the epithelial layer in the absence of calcium. These findings may provide a model for the physiologic action of calcium in epithelia such as the renal tubule.

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