Lung surfactant secretion by interalveolar Ca signaling

Ichimura, Hideo, Kaushik Parthasarathi, Jens Lindert, and Jahar Bhattacharya. Lung surfactant secretion by interalveolar Ca signaling. Am J Physiol Lung Cell Mol Physiol 291: L596–L601, 2006. First published May 12, 2006; doi:10.1152/ajplung.00036.2006.—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 Ca uncaging in intact alveoli of the isolated, blood-perfused rat lung. We loaded alveolar cells with the Ca cage o-nitrophenyl EGTA-AM (NP-EGTA-AM) together with the fluorophores, fluo 4, or LysoTracker green (LTG) to determine, respectively, the cytosolic Ca concentration ([Ca ]cyt) or type 2 cell secretion. To uncage Ca 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 [Ca ]cyt and induced secretion. Concomitantly, [Ca ]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 [Ca ]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 Ca signals regulate type 2 cell secretion in adjacent alveoli. Such interalveolar communication might facilitate acinar coordination of alveolar function.