FIGURE 7.

Schematic model for roles of K⁺ in EP processing and Ca²⁺ handling in Ca²⁺ transport. sE1PCa₂ is an E1PCa₂ species formed without K⁺ possessing a closed cytoplasmic gate and lumen-facing Ca²⁺ binding sites (an opened lumenal pathway) with high Ca²⁺ affinity (Fig. 6). sE1PCa₂ is in rapid equilibrium with the normal E1PCa₂. Here, s denotes silent because this species is apparently absent in the presence of K⁺ and also because the bound Ca²⁺ ions are not released to the cytoplasmic side even upon ADP-induced reverse dephosphorylation (to sE1Ca₂) in contrast to the normal E1PCa₂ reverse dephosphorylation. Actual active Ca²⁺ transport is achieved by a large reduction of the Ca²⁺ affinity during the normal sequence E1PCa₂ → E2PCa₂ → E2P + 2Ca²⁺ (blue arrows). The schematic is based on crystal structural models for the ADP-sensitive and -insensitive EP states and E1Ca₂, with the positions of the cytoplasmic N, P, and A domains, and membrane (orange layer) being approximate. The Ca²⁺ sites in the transmembrane domain are depicted as occluded (closed cytoplasmic and lumenal gates) in normal E1PCa₂, as lumen-facing and high Ca²⁺ affinity with the closed cytoplasmic gate in sE1PCa₂ and sE1Ca₂, and as lumenally opened with reduced Ca²⁺ affinity in E2P and E2PCa₂ (immediately before the Ca²⁺ release).