Anion interactions with CFTR and consequences for HCO3 transport in secretory epithelia

We have been studying CFTR channels in guinea pig pancreatic duct cells and rather surprisingly found that luminal HCO3- had a pronounced inhibitory effect on cAMP-activated CFTR chloride currents. The block produced by HCO3- was rapid, voltage-independent and occurred over a physiological range of extracellular HCO3-concentrations. I- and ClO4- were also found to inhibit CFTR currents, but both were less effective than HCO3-. Although we have not identified how HCO3-is able to block CFTR our data suggests that an external anion-binding site on the channel itself is involved. Overall, our results show that luminal HCO3-acts as a potent inhibitor of CFTR channels (and by inference CFTR-mediated secretion), under normal physiological conditions. These data have implications not only for current models of pancreatic duct cell HCO3-transport, but also for other bicarbonate-secreting tissues, such as the liver, GI tract and lungs.