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Gas channels

While studying pHi regulation in gastric parietal cells we found that the apical membrane has no detectable permeability to either CO2 or NH3—the first documented gas-impermeable membrane. This led us to rethink “Overton’s rule” and to describe the first gas channel aquaporin 1 (AQP1), which is not only permeable to H2O but also CO2. Others later showed that AQP1 is permeable to NH3, and that the rhesus (Rh) proteins are permeable to CO2 and NH3.

We developed an approach for using a large pH microelectrode to monitor the extracellular surface pH (pHS) on Xenopus oocytes exposed to CO2 or NH3. Initial pHS transients are indices of CO2 or NH3 permeability. Studying a wide range of AQPs and Rh proteins, we see that each has a characteristic CO2/NH3 permeability ratio—the first example of gas selectivity. Preliminary work suggests that NH3 moves only through AQP or Rh monomers, whereas CO2 generally prefers the central pore of the oligomer. Preliminary stopped-flow work with erythrocytes (RBCs) indicates that certain inhibitor combinations can block 75% of O2 efflux from RBCs—the first evidence for O2 channels.