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Lipopolysaccharide hyperpolarizes guinea pig airway epithelium by increasing the activities of the epithelial Na+ channel and the Na+ - K+ pump.

Authors
Dodrill-MW; Fedan-JS
Source
Am J Physiol, Lung Cell Mol Physiol 2010 Jul; 299(7):L550-L558
NIOSHTIC No.
20037746
Abstract
Earlier, we found that systemic administration of lipopolysaccharide (LPS; 4 mg/kg) hyperpolarized the transepithelial potential difference (Vt) of tracheal epithelium in the isolated, perfused trachea (IPT) of the guinea pig 18 h after injection. As well, LPS increased the hyperpolarization component of the response to basolateral methacholine, and potentiated the epithelium-derived relaxing factor-mediated relaxation responses to hyperosmolar solutions applied to the apical membrane. We hypothesized that LPS stimulates the transepithelial movement of Na+ via the epithelial sodium channel (ENaC)/Na+-K+ pump axis, leading to hyperpolarization of Vt. LPS increased the Vt-depolarizing response to amiloride (10 ÁM), i.e., offset the effect of LPS, indicating that Na+ transport activity was increased. The functional activity of ENaC was measured in the IPT after short-circuiting the Na+-K+ pump with basolateral amphotericin B (7.5 ÁM). LPS had no effect on the hyperpolarization response to apical trypsin (100 U/ml) in the Ussing chamber, indicating that channel-activating proteases are not involved in the LPS-induced activation of ENaC. To assess Na+-K+ pump activity in the IPT, ENaC was short-circuited with apical amphotericin B. The greater Vt in the presence of amphotericin B in tracheas from LPS-treated animals compared with controls revealed that LPS increased Na+-K+ pump activity. This finding was confirmed in the Ussing chamber by inhibiting the Na+-K+ pump via extracellular K+ removal, loading the epithelium with Na+, and observing a greater hyperpolarization response to K+ restoration. Together, the findings of this study reveal that LPS hyperpolarizes the airway epithelium by increasing the activities of ENaC and the Na+-K+ pump.
Keywords
Pulmonary-system-disorders; Enzyme-activity; Laboratory-animals; Respiratory-irritants; Lung-irritants; Mucous-membranes; Author Keywords: endotoxin; lung; airway epithelium; Na+ transport; transepithelial voltage
Contact
Jeffrey S. Fedan, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
APLPE7
Publication Date
20100716
Document Type
Journal Article
Email Address
jsf2@cdc.gov
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Issue of Publication
7
ISSN
1040-0605
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
American Journal of Physiology: Lung Cellular and Molecular Physiology
State
WV
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