title: Hypotonic shock modulates Na(+) current via a Cl(-) and Ca(2+)/calmodulin dependent mechanism in alveolar epithelial cells.
abstract: Alveolar epithelial cells are involved in Na(+) absorption via the epithelial Na(+) channel (ENaC), an important process for maintaining an appropriate volume of liquid lining the respiratory epithelium and for lung oedema clearance. Here, we investigated how a 20% hypotonic shock modulates the ionic current in these cells. Polarized alveolar epithelial cells isolated from rat lungs were cultured on permeant filters and their electrophysiological properties recorded. A 20% bilateral hypotonic shock induced an immediate, but transient 52% rise in total transepithelial current and a 67% increase in the amiloride-sensitive current mediated by ENaC. Amiloride pre-treatment decreased the current rise after hypotonic shock, showing that ENaC current is involved in this response. Since Cl(-) transport is modulated by hypotonic shock, its contribution to the basal and hypotonic-induced transepithelial current was also assessed. Apical NPPB, a broad Cl(-) channel inhibitor and basolateral DIOA a potassium chloride co-transporter (KCC) inhibitor reduced the total and ENaC currents, showing that transcellular Cl(-) transport plays a major role in that process. During hypotonic shock, a basolateral Cl(-) influx, partly inhibited by NPPB is essential for the hypotonic-induced current rise. Hypotonic shock promoted apical ATP secretion and increased intracellular Ca(2+). While apyrase, an ATP scavenger, did not inhibit the hypotonic shock current response, W7 a calmodulin antagonist completely prevented the hypotonic current rise. These results indicate that a basolateral Cl(-) influx as well as Ca(2+)/calmodulin, but not ATP, are involved in the acute transepithelial current rise elicited by hypotonic shock.
authors.affiliation: Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada ; Département de Médecine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: André
authors.initials: A
authors.lastname: Dagenais
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Tessier
authors.forename: Sabina
authors.initials: S
authors.lastname: Tatur
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Brochiero
authors.forename: Ryszard
authors.initials: R
authors.lastname: Grygorczyk
authors.forename: Yves
authors.initials: Y
authors.lastname: Berthiaume
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002147:Calmodulin / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D008297:Male; D009997:Osmotic Pressure; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D002712:Chlorides; D000255:Adenosine Triphosphate; D012964:Sodium; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium
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