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This Article Full Text Full Text (PDF) All Versions of this Article: 291/4/L596    most recent 00036.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Ichimura, H. Articles by Bhattacharya, J. Search for Related Content PubMed PubMed Citation Articles by Ichimura, H. Articles by Bhattacharya, J.

Lung surfactant secretion by interalveolar Ca²⁺ signaling

Lung Biology Laboratory, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, New York

Submitted 30 January 2006 ; accepted in final form 5 May 2006

Although clusters of alveoli form the acinus, which is the most distal respiratory unit, it is not known whether interalveolar communication coordinates acinar surfactant secretion. To address this, we applied real-time digital imaging in conjunction with photo-excited Ca²⁺ uncaging in intact alveoli of the isolated, blood-perfused rat lung. We loaded alveolar cells with the Ca²⁺ cage o-nitrophenyl EGTA-AM (NP-EGTA-AM) together with the fluorophores, fluo 4, or LysoTracker green (LTG) to determine, respectively, the cytosolic Ca²⁺ concentration ([Ca²⁺]_cyt) or type 2 cell secretion. To uncage Ca²⁺ from NP-EGTA, we exposed a region in a selected alveolus to high-intensity UV illumination. As a result, fluo 4 fluorescence increased, whereas LTG fluorescence decreased, in the photo-targeted region, indicating that uncaging both increased [Ca²⁺]_cyt and induced secretion. Concomitantly, [Ca²⁺]_cyt increases conducted from the uncaging site induced type 2 cell secretion in both the selected alveolus as well as in neighboring alveoli, indicating the presence of interalveolar communication. These conducted responses were inhibited by pretreating alveoli with the connexin43 (Cx43)-inhibiting peptides gap 26 and gap 27. However, although the conducted [Ca²⁺]_cyt increase diminished with distance from the uncaging site, type 2 cell secretion rates were similar at all locations. We conclude that Cx43-dependent, interalveolar Ca²⁺ signals regulate type 2 cell secretion in adjacent alveoli. Such interalveolar communication might facilitate acinar coordination of alveolar function.

cytosolic calcium; uncaging; lamellar body exocytosis; type 1 cell; type 2 cell

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