Mechanism of direct bicarbonate transport by the CFTR anion channel

Abstract

Cl(-) and HCO(3)(-) share a common transport pathway in CFTR, and selectivity between Cl(-) and HCO(3)(-) is independent of ionic conditions. The mechanism of transport is therefore effectively identical for both ions. We suggest that mutations in CFTR that cause cystic fibrosis by selectively disrupting HCO(3)(-) transport do not impair direct CFTR-mediated HCO(3)(-) transport, but may predominantly alter CFTR regulation of other HCO(3)(-) transport pathways.

Mechanisms of Bicarbonate Secretion: Lessons from the Airways

“…With a driving force of 5.8 mV, only 12 mS/cm 2 of the apical membrane conductance of 71 mS/ cm 2 is needed to account for the observed HCO 3 2 current of 65 mA/cm 2 . The conductance ratio of 12 mS/cm 2 to 71 mS/cm 2 is 0.17, and this too is consistent with the reported HCO 3 2 conductance compared with Cl 2 of the apical membrane of Calu-3 cells (Illek et al 1999) as well as CFTR (Linsdell et al 1997;Tang et al 2009;Man-song et al 2010). It must also be noted that a driving force of 5.8 mV does not explain the reported 80 mM concentration of HCO 3 2 in the thin film experiments Irokawa et al 2004).…”

“…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). Therefore, normal airway cells can secrete HCO 3 2 through CFTR, whereas CF cells show a HCO 3 2 impermeability.…”

Initial interrogation, confirmation and fine mapping of modifying genes: STAT3, IL1B and IFNGR1 determine cystic fibrosis disease manifestation

“…Cystic fibrosis (CF) is known as an autosomal recessively inherited disease caused by two defective copies of CFTR, 1 encoding a chloride [2][3][4] and bicarbonate [5][6][7][8] channel expressed in the apical membrane of epithelial cells. 1 Manifestation of this generalized exocrinopathy results from the CFTR-transmitted basic defect, described as altered chloride transport in CFTR-expressing tissues.…”

The Cystic Fibrosis of Exocrine Pancreas

“…Until very recently, the consensus was that the permeability ratio PHCO 3 2 /PCl 2 was .0.2 -0.4 in conditions with intracellular Cl 2 and pH values expected for most epithelia. A newer study also shows similar permeability ratio and it remains independent of ionic conditions (Tang et al 2009). …”