Ion channels of the lung and their role in disease pathogenesis

Abstract

Maintenance of normal epithelial ion and water transport in the lungs includes providing a thin layer of surface liquid that coats the conducting airways. This airway surface liquid is critical for normal lung function in a number of ways but, perhaps most importantly, is required for normal mucociliary clearance and bacterial removal. Preservation of the appropriate level of hydration, pH, and viscosity for the airway surface liquid requires the proper regulation and function of a battery of different types of ion channels and transporters. Here we discuss how alterations in ion channel/transporter function often lead to lung pathologies.

Keywords: chloride channels; oxidants; potasium channels; sodium channels.

Fig. 1.

Ion channels and transporters that participate in regulation of lung periciliary liquid (PCL) homeostasis and mucociliary clearance by ciliated airway epithelia. Apical membrane sodium reabsorption, accompanied by chloride secretion along with passive H₂O transport, provides the main mechanism responsible for PCL composition. The sodium reabsorption is mediated by coordinated function of epithelial sodium channel (ENaC, apical) and Na⁺-K⁺-ATPase (basal). However, apical cyclic nucleotide-gated channels (CNG) may contribute to sodium uptake as well. Furthermore, basal membrane located. CaCC, Ca²⁺-activated chloride channels; CFTR, cystic fibrosis transmembrane conductance regulator; TMEM, transmembrane domain; BK_Ca, large-conductance Ca²⁺-activated, voltage-dependent potassium channel; SK4, small-conductance Ca²⁺-activated potassium channels; NHE, Na⁺/H⁺ exchanger; NKCC, Na⁺-K⁺-Cl⁻ cotransporter; AE, anion exchanger; BORC, basolateral outward rectifying channel; BIRC, basolateral inward rectifying channel; BCFTR, basolateral CFTR-like channel; Kv7.1, α-subunit of a voltage-dependent potassium channel; K_Ca3.1, Ca²⁺-activated potassium channel.