Stochastic shielding and edge importance for Markov chains with timescale separation - Fig 2

(A) Colquhoun & Hawkes’ five-state model for the nicotinic acetylcholine (ACh) receptor [30]. White disks: closed (non-conducting) states (M_j = 0). Gray disks: open (conducting) states (M_j = 1). Nodes 1-5 (large black numbers) are defined in Table 1. Transitions 1-10 (small blue numbers) are defined in Table 2. The opening of the channel requires the binding of acetylcholine. Transitions 2, 6, and 10 are driven by ACh concentration. Transitions 3, 4, 7, 8 are directly observable through a conductance change. (B) Timescale separation (ratio of non-zero eigenvalues of the graph Laplacian) as a function of ACh concentration. (C) Edge importance R_k for k ∈ {1, …, 10} for each edge in the graph as a function of [ACh], see Eq 42. (D) Sample trace of the model exhibiting burstiness of the channel for low agonist concentration, here [ACh] = 0.5μM. (E) Zoomed in version of the burst in (D) labeled by the red arrow.