A model of the membrane pool interpretation of the effects of elevated [Ca2+]i on the nucleotide metabolism of RBCs in the absence of glycolytic substrates. The model portrays events related to the specific experimental protocol applied in this study. Addition of a high concentration of the Ca2+ ionophore A23187 established rapid Ca2+ equilibration across the RBC membrane, with saturating [Ca2+]i levels for the PMCA. The nucleotide pool available to the Ca2+ ATPase is diffusionally restricted from the bulk cell cytoplasm so that Ca2+ ATPase activity generated a sustained [ADP]/[ATP] concentration ratio that was higher within the membrane pool than in the bulk cell cytoplasm. The AK and AMPDA enzymes are assumed to be excluded from the membrane pool and confined to the cytoplasm. AMPDA activity is highly stimulated by elevated [Ca2+]i. The combined activity of the three enzymes (Ca2+ ATPase within the membrane pool and AK and AMPDA within the cytoplasmic compartment) generates ADP, AMP, and IMP at the expense of declining ATP along the time course and pattern documented in Fig. 4, with the minor decline in the total nucleotide content of the cells attributed to irreversible hypoxanthine formation from IMP. The likely physical localization of the functionally defined diffusion barrier in the space between inner membrane surface and cytoskeletal mesh, as suggested in previous depictions of the membrane pool (Hoffman, 1997), was left out of the diagram because the present results do not contribute any additional information on this point.