Epithelial Sodium Channels Play a Role in Air & Water Borne Diseases

Departments of Physiology and Pediatrics, Center for Developmental Lung Biology, School of Medicine, Emory University, USA

*Corresponding Author:

Charles A. Downs
Departments of Physiology and Pediatrics
Center for Developmental Lung Biology
School of Medicine, Emory University, USA
Tel: 404-727-4702
E-mail: Charles.downs@emory.edu

Received Date: May 10, 2012; Accepted Date: May 10, 2012; Published Date: May 11, 2012

Citation: Downs CA (2012) Epithelial Sodium Channels Play a Role in Air & Water Borne Diseases. Air Water Borne Dis 1:e109. doi:10.4172/2167-7719.1000e109

Copyright: © 2012 Downs CA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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The amiloride-sensitive epithelial sodium channel (ENaC) contributes to maintaining fluid homeostasis in the lung [1,2]. Excessive fluid accumulation in the alveolar space, as occurs with pneumonia or acute lung injury, compromises gas exchange and produces symptoms of breathlessness or dyspnea. Alveolar fluid clearance is driven by active transport of Na⁺, Cl^- and water from the airway lumen into the vascular space. ENaC is considered the rate limiting step in the net movement of fluid out of the alveolar space. Thus, strategies to enhance ENaC activity at the apical membrane are of interest in order to improve outcomes associated with diseases such as pneumonia and acute lung injury. ENaC in the airways is regulated by a variety of agents including G-coupled protein receptors (e.g. adrenergic, purinergic and dopaminergic), chemokines (TGF-β, TNF-α), reactive oxygen/nitrogen species (H₂O₂, O₂^.-, NO) and hormones (glucocorticoids). The multitude of regulatory pathways highlights the importance of ENaC in the lung [3-6].

Single channel electrophysiology measurements from lung tissue demonstrate that there are two types of ENaC—highly selective cation (HSC) and non-selective cation (NSC) channels. HSC ENaC channels preferentially transport Na+ (Na⁺/K⁺ selectivity >40) while NSC ENaC channels are less discriminant (Na⁺/K⁺ selectivity 1.4) [7]. In addition to differences in cation selectivity, HSC channels and NSC channels differ in their unitary conductance and other biophysical properties. However, they both play an important role in epithelial Na+ reabsorption. Alveolar type 2 (AT2) cells are best known for their role in surfactant production, but AT2 cells also contain both HSC and NSC ENaC channels. Activating ENaC in AT2 cells is useful in removing excess fluid; however, the type of channel activated can be affected by treatment— e.g. the type of β-adrenergic receptor stimulated—which may affect the resolution of edema. This is also true for alveolar type 1 (AT1) cells, the large flat epithelial cells that cover 95% of the alveolar surface area [8]. Many inflammatory cytokines reduce ENaC activity in the lung and may potentiate edema associated with focal or systemic infections. Additionally cytokines such as TNF-α may interfere with glucocorticoid gene activation preventing glucocorticoid mediated increases in ENaC activity [9,10].

ENaC function is of importance to the readers of Air & Water Borne Diseases because of the role of ENaC in Na+ reabsorption and subsequent resolution of edema. Edema is a defining feature of inflammation and occurs with bacterial, viral or fungal infections as well as acute and chronic exposure to toxicants. Understanding the type of ENaC (HSC vs. NSC) and the pathway (s) involved in Na+ transport continues to be an area of active research in determining fluid clearance associated with air and water borne diseases.

References

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