Fluid and electrolyte transport by cultured human airway epithelia.

Abstract

An understanding of the fluid and electrolyte transport properties of any epithelium requires knowledge of the direction, rate, and regulation of fluid transport and the composition of the fluid. Although human airway epithelia likely play a key role in controlling the quantity and composition of the respiratory tract fluid, evidence for such a role is not available. To obtain such knowledge, we measured fluid and electrolyte transport by cultured human nasal epithelia. Under basal conditions we found that epithelia absorbed Na+ and fluid; both processes were inhibited by addition of amiloride to the mucosal surface. These data suggest that active Na+ absorption is responsible for fluid absorption. Interestingly, Na+ absorption was not accompanied by the net absorption of Cl ; some other anion accompanied Na+. The combination of cAMP agonists and mucosal amiloride stimulated the secretion of NaCl-rich fluid. But surprisingly, the response to cAMP agonists in the absence of amiloride showed substantial intersubject variability: cAMP stimulated fluid secretion across some epithelia, for others, cAMP stimulated fluid absorption. The explanation for the differences in response is uncertain, but we speculate that the magnitude of apical membrane Na+ conductance may modulate the direction of fluid transport in response to cAMP. We also found that airway epithelia secrete H+ and absorb K+ under basal conditions; both processes were inhibited by cAMP agonists. Because the H+/K+-ATPase inhibitor, SCH 28080, inhibited K+ absorption, an apical membrane H+/K+-ATPase may be at least partly responsible for K+ and H+ transport. However, H+/K+ exchange could not entirely account for the luminal acidification. The finding that cAMP agonists inhibited luminal acidification may be explained by the recent finding that cAMP increases apical HCO3 conductance. These results provide new insights into how the intact airway epithelium may modify the composition of the respiratory tract fluid. (J.

Cystic Fibrosis: Does CFTR Malfunction Alter pH Regulation?

“…This was confirmed by Krouse et al [33] in the Ussing chamber with the addition that there existed a H-K ATPase to help neutralize some of the bicarbonate which was secreted. Such a mechanism had been previously reported by Smith and Welsh [27] in airway cells and again by Coakley et al [29] in primary airway cell cultures. In the same year Wu et al [94] published a paper showing an inwardly rectifying potassium channel (Kir4.2) in the apical membrane of Calu-3 cells and also in the apical membrane of freshly dissected airway submucosal glands.…”

“…The same thing happened when the calcium inside the cells was increased except a different set of anion channels were opened and bicarbonate can pass through in both normal and CF tissues. The following year Smith and Welsh [27] published a paper studying electrolyte transport in cultured airway epithelia cells. It was found that both normal and CF tissue secreted H+ in exchange for K+.…”

“…In this paper they posed the question, might HCO3-may play role in CF? A year later Welsh and Smith [27] reported their findings on how human epithelia cells control the quantity and composition of respiratory tract fluid. To do so they measured fluid and electrolyte transport by cultured human nasal epithelia and found that elevated cAMP stimulated fluid secretion across some epithelia, but for others the reverse, cAMP stimulated fluid absorption.…”

Thiocyanate Transport in Resting and IL-4-Stimulated Human Bronchial Epithelial Cells: Role of Pendrin and Anion Channels

“…Ϫ and HCO 3 Ϫ is important in the airway epithelium to control electrolyte and fluid secretion and to regulate pH (1)(2)(3). In particular, Cl Ϫ transport is recognized as one of the important factors in the regulation of airway surface hydration and therefore in mucociliary clearance (4).…”

A mouse model for the delta F508 allele of cystic fibrosis.

“…Therefore we used a novel targeting strategy to introduce the A\F508 mutation into the mouse CFTR gene (13) . Murine CFTR is 78% identical to human CFTR (14,15) and it contains a phenylalanine at residue 508 flanked by 28 amino acids identical to those in human CFTR. The goal of this work was to generate animals homozygous for the AF508 mutation (L/F/AF mice).…”