Transport of H2S and HS- across the human red blood cell membrane: rapid H2S diffusion and AE1-mediated Cl-/HS- exchange

The rates of H2S and HS- transport across the human erythrocyte membrane were estimated by measuring rates of dissipation of pH gradients in media containing 250 mu M H2S/HS-. Net acid efflux is caused by H2S/HS- acting analogously to CO2/HCO3- in the Jacobs-Stewart cycle. The steps are as follows: 1) H2S efflux through the lipid bilayer and/or a gas channel, 2) extracellular H2S deprotonation, 3) HS- influx in exchange for Cl-, catalyzed by the anion exchange protein AE1, and 4) intracellular HS- protonation. Net acid transport by the Cl-/HS-/H2S cycle is more efficient than by the Cl-/HCO3-/CO2 cycle because of the rapid H2S-HS- interconversion in cells and medium. The rates of acid transport were analyzed by solving the mass flow equations for the cycle to produce estimates of the HS- and H2S. transport rates. The data indicate that HS- is a very good substrate for AE1; the Cl-/HS- exchange rate is about one-third as rapid as Cl-/HCO3- exchange. The H2S permeability coefficient must also be high (>10(-2) cm/s, half time <0.003 s) to account for the pH equilibration data. The results imply that H2S and HS- enter erythrocytes very rapidly in the microcirculation of H2S-producing tissues, thereby acting as a sink for H2S and lowering the local extracellular concentration, and the fact that HS- is a substrate for a Cl-/HCO3 exchanger indicates that some effects of exogenous H2S/HS- may not result from a regulatory role of H2S but, rather, from net acid flux by H2S and HS- transport in a Jacobs-Stewart cycle.