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Lung surfactant secretion by interalveolar Ca2+ signaling
Hideo Ichimura1, Kaushik Parthasarathi, Jens Lindert
1Lung Biology Laboratory, Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, St. Luke's-Roosevelt Hospital Center, New York, NY 10019, USA.
Interalveolar communication coordinates surfactant secretion in the lung's smallest respiratory units. Calcium signals, transmitted via connexin43 (Cx43), regulate type 2 cell secretion in adjacent alveoli, suggesting coordinated acinar function.
Area of Science:
- Pulmonary physiology
- Cellular biology
- Biophysics
Background:
- The acinus, composed of alveoli clusters, is the lung's distal respiratory unit.
- The role of interalveolar communication in coordinating surfactant secretion within the acinus remains unclear.
Purpose of the Study:
- To investigate whether interalveolar communication coordinates surfactant secretion in the rat lung acinus.
- To elucidate the mechanisms underlying this communication.
Main Methods:
- Real-time digital imaging and photo-excited calcium (Ca2+) uncaging in isolated, blood-perfused rat lungs.
- Loading alveolar cells with Ca2+ indicators (NP-EGTA-AM, fluo 4) and secretion markers (LysoTracker green).
- Selective UV illumination to uncage Ca2+ and observe cellular responses.
Main Results:
- Uncaging Ca2+ increased cytosolic Ca2+ concentration ([Ca2+]cyt) and induced type 2 cell secretion in the targeted alveolus.
- Conducted [Ca2+]cyt increases triggered type 2 cell secretion in neighboring alveoli, demonstrating interalveolar communication.
- Connexin43 (Cx43)-inhibiting peptides blocked these conducted responses, implicating Cx43 in the communication.
Conclusions:
- Cx43-dependent, interalveolar Ca2+ signals regulate surfactant secretion in adjacent alveoli.
- This interalveolar communication likely facilitates coordinated acinar function, crucial for efficient gas exchange.
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