Figure 1. Voltage- and Ca²⁺-dependent activation of BK channels.

A, sequence alignment of S2–S4 in the voltage sensor domain of mSlo1 and K_V1.2 channels, highlighting the conserved charged residues (red and blue) that are important in voltage-dependent activation of both BK and K_V channels. The position of the last amino acid in each segment of mSlo1 is given (numbers). B, structure model of BK channels. The cartoon of the membrane-spanning domains only shows two subunits for clarity. The cytosolic domain is the tetrameric Slo1 structure (Yuan et al. 2010). The subunits are represented by different colours and the dark and light shades of each colour show the RCK1 and RCK2 structural domains within the same subunit (RCK: regulator for conductance of K⁺). A bound Ca²⁺ ion to the Ca²⁺ bowl in each subunit is shown as a red sphere. C, model of allosteric gating of BK channels by voltage and Ca²⁺. The channel can open and close (O and C) with an equilibrium constant L, which is modulated by the activation of four voltage sensors (R and A, with an equilibrium constant J) and the binding of four Ca²⁺ ions (a simplification from actual binding of eight Ca²⁺ ions, X and X-Ca²⁺, with a dissociation constant K) with the allosteric factor D and C, respectively. The voltage sensor activation and Ca²⁺ binding also affect each other with a factor E. The model was proposed by Horrigan & Aldrich (2002).