binding of the "red square" ligand (Na+, positively charged) increases the probability that the "green hexagon" ligand (e.g., glucose) also binds
obviously, the opposite also is true: hexagon bound, square more likely to bind
Na+ outside the cell (red=positive) will favour the binding of another substrate (gree hexagon: glucose, aminoacid, chloride...)
when this happens, the transporter (fully loaded) will rapidly shuttle to the other side, because Na+ pushes to get in (negative potential inside, blue)
once the binding sites are exposed inside, the transporter does not tend to shuttle back (negative potential retains the sodium ion)
sooner or later Na+ will detach, due to the low internal [Na+]
the transporter loses affinity for the other substrate, which detaches, so that the transporter can shuttle back (it only shuttles either fully loaded or empty)
the change in affinity for the substrate depends on Na+ binding
Na+ concentration ratio produces different occupation of the binding site on the two sides: → different affinity for the substrate
[Na+] ratio (≈ 12-fold) corresponds to a ΔG = RT·ln(12), i.e. about 2.5 RT, which can produce a 12-fold concentration of the other substrate
since the transporter, when loaded, has a very short life on the outside (because Na+ pushes to enter) and a long one on the inside, the probability of Na+ and the substrate binding on the outside and leaving on the inside is
further increased
the substrate can therefore be concentrated much more than 12-fold