Selective response of human airway epithelia to luminal but not serosal solution hypertonicity. Possible role for proximal airway epithelia as an osmolality transducer.

Abstract

The response of cultured human nasal epithelia to hypertonic bathing solutions was tested using ion-selective microelectrode and quantitative microscopy. Raised luminal, but not serosal, osmolality (±150 mM mannitol) decreased Na' absorption but did not induce Cl-secretion. Raised luminal osmolality increased cell Cl-activity, Na' activity, and transepithelial resistance and decreased both apical and basolateral membrane potentials and the fractional resistance of the apical membrane; equivalent circuit analysis revealed increases in apical, basolateral, and shunt resistances. Prolonged exposure (10 min) to 430 mosM luminal solution elicited no regulation of any parameter. Optical measurements revealed a reduction in the thickness of preparations only in response to luminal hypertonic solutions. We conclude that (a) airway epithelial cells exhibit asymmetric water transport properties, with the apical membrane water permeability exceeding that of the basolateral membrane; (b) the cellular response to volume loss is a deactivation of the basolateral membrane K+ conductance and the apical membrane Cl-conductance; (c) luminal hypertonicity slows the rate of Na' absorption but does not induce Cl-secretion; and (d) cell volume loss increases the resistance of the paracellular path. We speculate that these properties configure human nasal epithelium to behave as an osmotic sensor, transducing information about luminal solutions to the airway wall. (J. Clin. Invest. 1994. 94:779-787.)

Hypertonic saline alters ion transport across the human airway epithelium

“…Further studies will be necessary to deter- mine whether luminal mannitol does alter ion transport in vivo, with similar but opposite effects resulting in no significant overall response. However, the responses to luminal saline appear to differ in the two studies with a significant decrease in nasal PD in the current study contrasting with the lack of change in Vt found by WILLUMSEN et al [11]. This may simply reflect the different doses used in the respective studies -the only dose reported in the WILLUMSEN et al study was 75 mM, whilst the smallest dose used in the current study was 150 mM.…”

“…Addition of 150 mM mannitol to the luminal surface was associated with decreases (less negative) in both apical (Va) and basolateral (Vb) membrane potentials, with small but variable effects on the transepithelial membrane potential (Vt) in different monolayers. Addition of 75 mM NaCl to the luminal solution also decreased both Va and Vb, but did not alter Vt [11]. The nonsignificant increase in nasal PD found in the current study corresponds with the variable effects on Vt found in the nasal polyp monolayers; Va and Vb cannot be assessed using the nasal PD technique.…”

“…In monolayers of cultured human nasal polyp cells, WILLUMSEN et al [11] measured the effects of raised luminal and serosal osmolality. Addition of 150 mM mannitol to the luminal surface was associated with decreases (less negative) in both apical (Va) and basolateral (Vb) membrane potentials, with small but variable effects on the transepithelial membrane potential (Vt) in different monolayers.…”

Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation

“…Identification of AQP5 expression in bronchial epithelial cells strongly implicates AQP5 as the previously described, but unidentified mercury-sensitive water channel responsible for mediating osmotically driven transcellular water flow and airway surface liquid composition (28,29). It has been shown that a local increase in the osmolarity of the airway surface liquid as a result of respiratory water loss or inhalation of hypertonic saline induces bronchoconstriction in asthmatic patients (30,31).…”

Mucociliary clearance during and after isocapnic hyperventilation with dry air in the presence of frusemide

“…The RVI can take up to 20 min to be complete [25,26]. There is evidence that the apical membrane of the airway epithelium is more permeable to water than the basolateral membrane [29]. There is also evidence that asthmatic subjects have thickening of the basement membrane [30,31], which could limit the rate of water diffusion when there is a high demand.…”