![Figure 1. Constructing a voltage- and ligand-activated BK-like ion channel. (A) A two-state channel with only a pore (P) domain undergoing a conformational transition between closed (C) and open (O) states, as governed by the L equilibrium constant (L = Loexp(−zV/RT)). (B) The same channel, to which a voltage-sensing (V) or ligand-binding (S) gating domain has been added. Transitions of voltage sensors between rest (R) and activated (A) states are manifested by the domain equilibrium constant J (= Joexp(−zV/RT)), whereas K (= Ka[S], where Ka is the association constant) reflects the transition of the S domain between the unbound (U) and bound (B) states. The fourth power in the equilibrium or interaction constants reflects the tetrameric organization of the voltage- or ligand-gated channels undergoing independent and sequential gating charge and ligand-binding transitions, respectively (Monod et al., 1965). The d and c interdomain interaction constants reflect the ratio of the equilibrium constants for V activation in the open and closed states (d), or the ratio of ligand affinity to the open and closed conformations (c). Resting and final open states are colored red. (C) The same channel as in B to which a voltage-sensing or ligand-binding gating domains has been added (as required) to yield a dually voltage- and ligand-activated BK-like channel. The interaction constant e represents the coupling between the voltage and ligand-binding domains (left face of the cube), whereas the a coupling constant represents the coupling between the pore and the ligand-binding domain, where the V domain has already been activated (back face of the cube). The dashed red arrow indicates the overall channel equilibrium constant (KCnet), indicative of the resting to final open-state transition (CRU→OAB transition). The equilibrium constants of any transition along the thermodynamic cube are indicated next to the arrows. Arrows in these schemes are drawn to indicate possible paths that can be taken, although all represent equilibrium between the states connected.](https://cdn.rupress.org/rup/content_public/journal/jgp/141/1/10.1085_jgp.201210929/4/jgp_201210929_fig1.jpeg?Expires=1771860172&Signature=nPV9VWY67PA01CuawUdERzV1UoClMh9q6QdnHj2~mXx6AQKt1wdvD3g7ciVv17txlvmdtBpqb3V~E7Aoe9kdDqt2~gaDFKS9ahlVy6UDoKdnSrp~PUzPGrmxa4MC0ToO1lLwzNT6rnbkNanv5Bm2Utv7v8Qn2vIFqT0ENdvHdBbB7eVMW75feIoK2IyXXkFd2Y-2tasIdOk~9Zz51DAwBId-D7gWyC3ywCZ136Kz~W43LZC~H~dY8F0e-s9BzidpQirTWkl5fToIy~1n4anWAmYq7YX1k3BmafqjkSt2KbuWKtKQViTTPwkuG32Aj74o2UfRrWN-UPfnnwz5jNGy7Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Constructing a voltage- and ligand-activated BK-like ion channel. (A) A two-state channel with only a pore (P) domain undergoing a conformational transition between closed (C) and open (O) states, as governed by the L equilibrium constant (L = Loexp(−zV/RT)). (B) The same channel, to which a voltage-sensing (V) or ligand-binding (S) gating domain has been added. Transitions of voltage sensors between rest (R) and activated (A) states are manifested by the domain equilibrium constant J (= Joexp(−zV/RT)), whereas K (= Ka[S], where Ka is the association constant) reflects the transition of the S domain between the unbound (U) and bound (B) states. The fourth power in the equilibrium or interaction constants reflects the tetrameric organization of the voltage- or ligand-gated channels undergoing independent and sequential gating charge and ligand-binding transitions, respectively (Monod et al., 1965). The d and c interdomain interaction constants reflect the ratio of the equilibrium constants for V activation in the open and closed states (d), or the ratio of ligand affinity to the open and closed conformations (c). Resting and final open states are colored red. (C) The same channel as in B to which a voltage-sensing or ligand-binding gating domains has been added (as required) to yield a dually voltage- and ligand-activated BK-like channel. The interaction constant e represents the coupling between the voltage and ligand-binding domains (left face of the cube), whereas the a coupling constant represents the coupling between the pore and the ligand-binding domain, where the V domain has already been activated (back face of the cube). The dashed red arrow indicates the overall channel equilibrium constant (), indicative of the resting to final open-state transition (CRU→OAB transition). The equilibrium constants of any transition along the thermodynamic cube are indicated next to the arrows. Arrows in these schemes are drawn to indicate possible paths that can be taken, although all represent equilibrium between the states connected.
