Hypothesis: do voltage-gated H⁺channels in alveolar epithelial cells contribute to CO₂ elimination by the lung?

Although alveolar epithelial cells were the first mammalian cells in which voltage-gated H⁺ currents were recorded, no specific function has yet been proposed. Here we consider whether H⁺ channels contribute to one of the main functions of the lung: CO₂ elimination. This idea builds on several observations: 1) some cell membranes have low CO₂permeability, 2) carbonic anhydrase is present in alveolar epithelium and contributes to CO₂ extrusion by facilitating diffusion, 3) the transepithelial potential difference favors selective activation of H⁺ channels in apical membranes, and 4) the properties of H⁺ channels are ideally suited to the proposed role. H⁺channels open only when the electrochemical gradient for H⁺ is outward, imparting directionality to the diffusion process. Unlike previous facilitated diffusion models, ${HCO}_3^{-}$ and H⁺ recombine to form CO₂ in the alveolar subphase. Rough quantitative considerations indicate that the proposed mechanism is plausible and indicate a significant capacity for CO₂ elimination by the lung by this route. Fully activated alveolar H⁺ channels extrude acid equivalents at three times the resting rate of CO₂ production.