Figure 2. . Mechanisms of interaction between voltage sensors and Ca2+-binding sites. (A1) If the binding of Ca2+ to a single subunit affects voltage sensors equally then voltage sensor equilibrium constants in all four subunits will increase E-fold to JE as indicated. (A2) In Scheme II, we assume Ca2+ binding only affects the voltage sensor in the same subunit. Consequently, the A2 mechanism predicts more states than the A1 mechanism. (B) For example, when a channel has two Ca2+-bound (open circles) and two voltage sensors activated (open squares), the A2 mechanism specifies three states depending on the relative location of Ca2+ and activated voltage sensors. That the states are functionally distinct can be seen by comparing the different Ca2+-binding equilibria for the unoccupied binding sites (K,K), (K,KE), and (KE,KE). Equilibrium constants for voltage sensor activation are also different. By contrast, the A1 mechanism specifies a single state with equilibrium constants KE2 for Ca2+ binding and JE2 for voltage sensor activation (not depicted).
Image published in: Horrigan FT and Aldrich RW (2002)
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