VSD-I time course of activation follows ionic current kinetics. (A and B) The activation kinetics of ionic current (black symbols) and of each VSD (colored symbols) were well described by the sum of two exponential functions (τ_fast, empty symbols; τ_slow, filled symbols). In the plots, fast and slow time constants (A) and their relative amplitudes (B) are compared for each individual VSD with those of the ionic current. Note that all domains share with the pore a kinetic component with τ_slow ∼100 ms. However, only VSD-I exhibits a fast component compatible with that of the ionic current; the other VSDs display a τ_fast approximately fivefold faster, likely more suitable for RYR1 activation.