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

Abstract

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, [Formula: see text] 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.