Apparent allosteric competitive inhibition of Ca²⁺ binding by H⁺ in MthK channels. H ([H⁺]/K_H) and K ([Ca²⁺]/K_C) represent the equilibrium constants for H⁺ and Ca²⁺ binding, respectively. E represents the allosteric coupling factor between H⁺ binding and Ca²⁺ binding (E < 1). The binding of H⁺ drives the Ca²⁺-dependent equilibrium constant away from the Ca²⁺/H⁺-bound states; likewise, the binding of Ca²⁺ drives the H⁺-dependent equilibrium constant away from the Ca²⁺/H⁺-bound states. Because Ca²⁺ binding is coupled to channel opening (not depicted here), this action of H⁺ effectively inhibits MthK opening. Although the binding sites for H⁺ and Ca²⁺ are depicted separately here, we cannot rule out the possibility that the binding sites for H⁺ and Ca²⁺ partially overlap.