Fig. 1.

Cartoon representing three- and four-state models for Na⁺ binding to SGLT1. For clarity of presentation, we assume the number (n) of Na⁺ ions binding to the empty transporter is 2. The ligand-free protein carries a net negative charge and transient capacitive SGLT1 currents are associated with reorientation of the empty transporter between external and internal membrane surfaces (C1 C6) and Na⁺ binding/dissociation (C1 + 2Na⁺ C2Na₂ for the three-state and C1+Na⁺ C1Na + Na⁺ C2Na₂ for the four-state model). K_d is the lumped sodium dissociation constant for the three-state model, and K_dA and K_dB are the sodium dissociation constants for the first and second binding sites for the four-state model (Theory section). Hyperpolarizing voltages drive the transporter to the outward conformation (C6 → C1), as well as promoting the transition C1 → C2Na₂.