Adrenergic Regulation of Ion Transport Across Adult Alveolar Epithelial Cells: Effects on Cl− Channel Activation and Transport Function in Cultures with an Apical Air Interface

In this review, we discuss evidence that supports the hypothesis that adrenergic stimulation of transepithelial Na absorption across the alveolar epithelium occurs indirectly by activation of apical Cl channels, resulting in hyperpolarization and an increased driving force for Na uptake through amiloride-sensitive Na channels. This hypothesis differs from the prevailing idea that adrenergic-receptor activation increases the open probability of Na channels, leading to an increase in apical membrane Na permeability and an increase in Na and fluid uptake from the alveolar space. We review results from cultured alveolar epithelial cell monolayer experiments that show increases in apical membrane Cl conductance in the absence of any change in Na conductance after stimulation by selective β-adrenergic-receptor agonists. We also discuss possible reasons for differences in Na-channel regulation in cells grown in monolayer culture compared with that in dissociated alveolar epithelial cells. Finally, we describe some preliminary in vivo data that suggest a role for Cl-channel activation in the process of amiloride-sensitive alveolar fluid absorption.

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Dome formation in primary cultured monolayers of alveolar epithelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.1982.243.1.c96 ◽

1982 ◽

Vol 243 (1) ◽

pp. C96-C100 ◽

Cited By ~ 86

Author(s):

B. E. Goodman ◽

E. D. Crandall

Keyword(s):

Epithelial Cells ◽

Life Span ◽

Fluid Balance ◽

Alveolar Epithelial Cells ◽

Type Ii ◽

Transport Function ◽

Dome Formation ◽

Alveolar Epithelial ◽

Free Air

We have observed the formation of domes by type II alveolar epithelial cells harvested from rat lungs. The cells were harvested using elastase and grew to confluence in 3-4 days after plating on plastic. Numerous domes were observed in the monolayers 4-18 days after plating, with peak dome density occurring at days 6-9. When trypsin was used instead of elastase as the harvesting enzyme, many fewer domes were formed by the monolayers, with peak dome density observed at day 5 and no domes seen after 8 days. The life span of an individual dome was about 3-4 h. The presence of domes indicates an intact active transport function of the cells in the monolayer, which may represent an important mechanism for the maintenance of fluid-free air spaces and normal alveolar fluid balance in mammalian lungs in vivo.

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Hypoxia-Effects on Cai-Signaling and Ion Transport Activity of Lung Alveolar Epithelial Cells

Cellular Physiology and Biochemistry ◽

10.1159/000047805 ◽

2001 ◽

Vol 11 (4) ◽

pp. 187-196 ◽

Cited By ~ 11

Author(s):

Marike Papen ◽

Ralf Wodopia ◽

Peter Bärtsch ◽

Heimo Mairbäurl

Keyword(s):

Epithelial Cells ◽

Ion Transport ◽

Alveolar Epithelial Cells ◽

Transport Activity ◽

Alveolar Epithelial

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G protein-regulated large-conductance chloride channels in freshly isolated fetal type II alveolar epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1993.265.4.l323 ◽

1993 ◽

Vol 265 (4) ◽

pp. L323-L329 ◽

Cited By ~ 6

Author(s):

P. J. Kemp ◽

G. G. MacGregor ◽

R. E. Olver

Keyword(s):

Epithelial Cells ◽

G Protein ◽

Alveolar Epithelial Cells ◽

Disulfonic Acid ◽

Single Channels ◽

Type Ii ◽

Channel Activity ◽

Patch Clamp Technique ◽

Alveolar Epithelial ◽

Cl Channel

Using the patch-clamp technique, we have recorded single channels in cell-attached and inside-out excised patches from the plasma membrane of type II alveolar epithelial cells freshly isolated from fetal guinea pig lung by elastase digestion and differential filtration. In cell-free patches the channels were highly selective for Cl- (PCl:Pcat = 9:1), had a large unitary conductance (375 pS +/- 23 pS), and current reversal of 0 mV in either symmetrical Na(+)-rich solutions or when the inner membrane leaflet was bathed in a K(+)-rich solution. The large-conductance Cl- channel exhibited little or no voltage inactivation at positive potentials, remained open for a significant amount of time at potentials negative to -40 mV, and was blocked at all potentials by 0.1 mM 4-acetamido-4-isothiocyanostilbene-2,2-disulfonic acid. Channel activity was independent of intracellular calcium concentration. Bath addition of the nonmetabolizable analogue of GTP, GTP gamma S (0.1 mM), caused a voltage-dependent inhibition of channel activity [open probability (Po) plot was shifted by at least +25 mV]. Smaller channels (25 +/- 3 pS) were recorded in the cell-attached configuration with a current-voltage (I-V) relationship which was compatible with a Cl- conductance. On excision, the patches previously containing small-conductance channels exhibited only large-conductance Cl- channel behavior. These large-conductance, G protein-regulatable Cl- channels may provide a route for alveolar cell Cl- exit and as such may be an integral part of the mechanism responsible for secretion of fetal lung fluid.

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β2-Adrenergic Stimulation Blunts Inhibition of Epithelial Ion Transport by Hypoxia of Rat Alveolar Epithelial Cells

Cellular Physiology and Biochemistry ◽

10.1159/000272057 ◽

2010 ◽

Vol 25 (001) ◽

pp. 123-134 ◽

Cited By ~ 10

Author(s):

Benjamin Loeh ◽

Emel Baloglu ◽

Alberto Ke ◽

Peter Bärtsch ◽

Heimo Mairbäurl

Keyword(s):

Epithelial Cells ◽

Ion Transport ◽

Alveolar Epithelial Cells ◽

Adrenergic Stimulation ◽

Alveolar Epithelial ◽

Epithelial Ion Transport

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Possible role of ROS as mediators of hypoxia-induced ion transport inhibition of alveolar epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2000.278.4.l640 ◽

2000 ◽

Vol 278 (4) ◽

pp. L640-L648 ◽

Cited By ~ 16

Author(s):

Wolf Heberlein ◽

Ralf Wodopia ◽

Peter Bärtsch ◽

Heimo Mairbäurl

Keyword(s):

Epithelial Cells ◽

Ion Transport ◽

A549 Cells ◽

Alveolar Epithelial Cells ◽

Transport Activity ◽

Excitable Cells ◽

Alveolar Epithelial ◽

Oxygen Sensitive ◽

Na Uptake

In oxygen-sensitive excitable cells, responses to hypoxia are initiated by membrane depolarization due to closing of the K channels that is thought to be mediated by a decrease in reactive oxygen species (ROS). Because the mechanisms of hypoxic inhibition of ion transport of alveolar epithelial cells (Planes C, Friedlander G, Loiseau A, Amiel C, and Clerici C. Am J Physiol Lung Cell Mol Physiol 271: L70–L78, 1996; Mairbäurl H, Wodopia R, Eckes S, Schulz S, and Bärtsch P. Am J Physiol Lung Cell Mol Physiol 273: L797–L806, 1997) are not yet understood, we tested the possible involvement of a hypoxia-induced change in ROS that might control transport activity. Transport was measured as86Rb and22Na uptake in A549 cells exposed to normoxia, hyperoxia, or hypoxia together with ROS donors and scavengers. H2O2< 1 mM did not affect transport, whereas 1 mM H2O2activated22Na uptake (+200%) but inhibited86Rb uptake (−30%). Also hyperoxia, aminotriazole plus menadione, and diethyldithiocarbamate inhibited86Rb uptake. N-acetyl-l-cysteine, diphenyleneiodonium, and tetramethylpiperidine- N-oxyl, used to reduce ROS, inhibited86Rb uptake, thus mimicking the hypoxic effects, whereas deferoxamine, superoxide dismutase, and catalase were ineffective. Also, hypoxic effects on ion transport were not prevented in the presence of H2O2, diethyldithiocarbamate, and N-acetyl-l-cysteine. These results indicate that ion transport of A549 cells is significantly affected by decreasing or increasing cellular ROS levels and that it is possible that certain species of ROS might mediate the hypoxic effects on ion transport of alveolar epithelial cells.

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