Figure 9: Markov state modelling of AC-1 inhibition.
Markov state modelling was used to simulate current traces under control and 300 nM AC-1. The state model as indicated in a was used. The rate constants (in s−1) had the following voltage dependence (φ=VF/RT) (where V is the membrane voltage, F Faraday’s constant, R the gas constant and T absolute temperature): α1=exp(0.47 φ); β1=0.2 × exp(−0.35 φ); α2=0.46 × exp(0.47 φ); β2=3.3 × exp(−0.35 φ); α3=24 × exp(0.06 φ); β3=19 × exp(−0.007 φ); ɛ=4.6 × exp(0.8 φ); δ=1.4 × exp(−0.7 φ); γ=10. For unbound channels ρ=10, and for AC-1 bound channels ρ=0.1. The voltage protocol used to simulate the traces shown in the figure was: holding potential −80 mV, steps from −40 to +60 mV in 20 mV steps for 5 s, tail potential −120 mV. Simulated traces are shown in (b). Simulated normalized peak inward tail currents at −120 mV are plotted as a function of the prepulse potential (5 s pulses, control in black and AC-1 in red circles c).
