Controversies surrounding the role of CFTR in airway bicarbonate secretion

Abstract

Bicarbonate (HCO3−) serves many functions in the human body. It is an important biological buffer required for maintaining intracellular and extracellular acid–base balance, and plays a key role in CO2 transport by blood. Less well known is that HCO3− is secreted onto the mucosal surface of most epithelia where it is involved in a myriad of vital processes including sperm capacitation, innate defence, mucin expansion and mucosal protection. An important challenge in epithelial biology has been to understand the molecular coordination of transepithelial HCO3− secretion and how this simple anion impacts on such a wide variety of physiological processes. Through studies on the inherited disease cystic fibrosis (CF), it has become clear that the plasma membrane protein encoded by the CF gene, cystic fibrosis transmembrane conductance regulator (CFTR), is essential for epithelial HCO3− secretion, but only recently have we begun to fully appreciate the complex role that CFTR plays in this process.