Scheme of a structurally relevant, allosteric model of Ca_V activation, accounting for both time- and voltage-dependent properties of VSD activation and pore opening. See Pantazis et al. (2014), Savalli et al. (2016), and Allosteric model of Ca_V... Briefly, each VSD and the pore (equilibrium constant J and L) are modeled as two-state particles, undergoing resting (R)–active (A), or closed (C)–open (O), voltage-dependent transitions, respectively. VSD activation allosterically stabilizes the pore open state by coupling energy W.