Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation.

Abstract

The transepithelial potential difference (PD) of cystic fibrosis (CF) airway epithelium is abnormally raised and the Cl-permeability is low. We studied the contribution of active Na' absorption to the PD and attempted to increase the Cl-permeability of CF epithelia. Nasal epithelia from CF and control subjects were mounted in Ussing chambers and were short-circuited. The basal rate of Na' absorption was raised in CF polyps compared with control tissues. Whereas beta agonists induced Cl-secretion in normal and atopic epithelia, beta agonists further increased the rate of Na' absorption in CF epithelia without inducing Clsecretion. This unusual effect is not due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelia. We conclude that CF airway epithelia absorb Na' at an accelerated rate. The abnormal response to beta agonists may reflect a primary abnormality in a cAMP-modulated path, or a normal cAMP-modulated process in a Cl-impermeable epithelial cell.

Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium

“…Although regulatory pathways that involve cyclic AMP and Ca2+ phospholipid-dependent protein kinases are defective in CF airway epithelium (Boucher et al, 1986), a recent report indicates that Ca2+-dependent Cl-secretory regulatory mechanisms are retained by CF epithelia . Our data show [Ca21]i was increased and CPsecretion stimulated by ATP and UTP in CF airway epithelial cells pretreated with amiloride.…”

Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis

“…42,43 Electrolyte transport defects in the CF airway epithelium have been extensively characterized in CF nasal epithelia, both in vitro and in vivo. [44][45][46] Such studies have demonstrated that, in addition to a defective cAMP inducible chloride secretory response, CF nasal epithelia have increased levels of amiloride-sensitive Figure 2 Model for cellular compartmentalization of CFTR expression and function in the airway. The level of CFTR expression in the airway is highly regulated within different cell types.…”

Mechanisms of Bicarbonate Secretion: Lessons from the Airways

“…Indeed, only after Na þ transport is down-regulated or inhibited with amiloride is it possible to observe Cl 2 secretion in normal cells. It is generally accepted that the difference in V ap between normal and CF cells is due to the loss of CFTR channels and the higher Na þ permeability in CF cells (Boucher et al 1986(Boucher et al , 1988Boucher 1994a,b). Besides Cl 2 , CFTR also conducts HCO 3 2 , as shown in the studies of Gray et al (1990) and Linsdell and coworkers (Linsdell et al 1997;Tang et al 2009;Li et al 2011) and more recently by Ishiguro et al (2009).…”