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. 2024 Oct 9;18(1):2402749. doi: 10.1080/19336950.2024.2402749

Figure 1.

The figure contains six different Markov models. All are star-shaped with a single open state in the center and all closed states directly connected to the open state. Panel A has the full model with five closed states and the blocked state B. In panels B-F, some states are fused, reducing the number of closed states.

Markov models used for the fitting of the blocking kinetics. (a) The full Markov model with all states as known so far from previous studies [2,3,29] supplemented by the blocked state B. The states C1, C2 and C3 belong to slow gating with dwell times longer than a millisecond, with C3 occurring only in KcvS due to its cytosolic gate [2]. These states can be analyzed by a jump detector and dwell time analysis. F and M belong to fast gating (dwell-time in F about 5 µs) and medium gating (dwell-time in M is voltage-dependent ranging between 150 µs to 40 µs) [3]. (b, c) The models used for the analysis of fast blockers. C1 - C3 cannot be resolved by the beta distribution analysis and are merged into S (“slow”). (c) For TEA, B has a similar dwell time as F, so the two states cannot be kinetically separated. (b) for TPrA, this separation is possible [7]. (d,e,f) in the experiments with slow blockers, the dwell time in B coincides with one of the slow states C1 - C3. Thus, only two (KcvNTS) or three (KcvS) closed states are detected in the dwell time histograms. The inclusion of B is identified by concentration dependence. O,F,M are merged into an apparent open state O*. Definition: The rate constant of the transition from a state X to a state Y is called kXY. kBO as the rate constant of blocker dissociation is also called koff.