Carbon dioxide transport across membranes

Carbon dioxide (CO₂) movement across cellular membranes is passive and governed by Fick's law of diffusion. Until recently, we believed that gases cross biological membranes exclusively by dissolving in and then diffusing through membrane lipid. However, the observation that some membranes are CO₂ impermeable led to the discovery of a gas molecule moving through a channel; namely, CO₂ diffusion through aquaporin-1 (AQP1). Later work demonstrated CO₂ diffusion through rhesus (Rh) proteins and NH₃ diffusion through both AQPs and Rh proteins. The tetrameric AQPs exhibit differential selectivity for CO₂ versus NH₃ versus H₂O, reflecting physico-chemical differences among the small molecules as well as among the hydrophilic monomeric pores and hydrophobic central pores of various AQPs. Preliminary work suggests that NH₃ moves through the monomeric pores of AQP1, whereas CO₂ moves through both monomeric and central pores. Initial work on AQP5 indicates that it is possible to create a metal-binding site on the central pore's extracellular face, thereby blocking CO₂ movement. The trimeric Rh proteins have monomers with hydrophilic pores surrounding a hydrophobic central pore. Preliminary work on the bacterial Rh homologue AmtB suggests that gas can diffuse through the central pore and three sets of interfacial clefts between monomers. Finally, initial work indicates that CO₂ diffuses through the electrogenic Na/HCO₃ cotransporter NBCe1. At least in some cells, CO₂-permeable proteins could provide important pathways for transmembrane CO₂ movements. Such pathways could be amenable to cellular regulation and could become valuable drug targets.