Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is Crucial for CO2 Signal Transduction in Avian Intrapulmonary Chemoreceptors (IPC)

Abstract

CFTR is an anion channel and ABC transmembrane protein which also modulates other anion channels and transporters. Since CFTR is widely expressed in cells that transport anions, and we hypothesize that anion transport in IPC is critical for CO2 transduction, we tested for the presence of CFTR in IPC. Glibenclamide, a non‐selective CFTR inhibitor, and CFTR‐172inh, a highly specific CFTR inhibitor were given separately to pentobarbital‐anesthetized mallards (Anas platyrhynchos, n =15) while recording single cell IPC spike train responses to inspired CO2 steps (0%–7%, 11sec period). Both drugs produced similar results, where IPC discharge with the lowest 2 μmol/kg doses was unchanged from control, while the 4 and 8 μmol/kg doses significantly decreased both mean IPC discharge and phasic adaptation (ANOVA, p<0.01). IPC CO2 sensitivity was completely abolished in 4 CFTR‐172inh experiments and 4 glibenclamide experiments. Results suggest that CFTR is a crucial anion regulating channel involved in IPC CO2 signal transduction.Support or Funding InformationSupport: NIH R15 HL087269‐02.