A Markov model of Ca_v2.3 channel gating. (A) Topology of a Markov model that accounts for most salient features of Ca_v2.3 channel gating under control conditions. Horizontal transitions are voltage dependent and correspond to movement of four nonidentical voltage sensors and channel opening or closing, with rate constants expressed in terms of the transition state theory (for details, see text). Vertical transitions are voltage independent and correspond to entry into and return from fast (middle) and slow (bottom) inactivated states. Transitions between inactivated states are identical to the parallel transitions between closed and open states. (B) Overview of individual transitions of the model and optimized parameter values obtained by globally fitting the model to the whole set of control recordings obtained with 4 mM Ca²⁺ at pH 7.4. (C–F) Comparison of recorded (black) and simulated (turquoise) families of current traces evoked with the protocols depicted above. Source code for the model is available in ModelDB (McDougal et al., 2017) at http://modeldb.yale.edu/261714.