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. 2022 Apr 12;12(4):570. doi: 10.3390/biom12040570

Figure 4.

Figure 4

Allosteric gate model simulation of the inhibition of HCN4 channels by propofol. (A) The allosteric gate model for HCN channel activation, where L, H(V), K are the equilibrium constants for the transitions between close and open (C–O) or rest and active (R–A) states in the PD, VSD, and CNBD, respectively. F, C, and E are the allosteric coupling factors between the PD and the VSD, between the PD and CNBD, and between the VSD and CNBD, respectively. (B) Model fitting to the PO-V data in the presence and absence (control) of propofol, obtained by normalizing the current density (relative PO ) to the maximum value in control. The best-fit parameters of F, C, and E are 8.2, 1.6, and 1.6, respectively, in controls, and became 7.8, 2.9, and 1.3, respectively, in the presence of propofol. (C) Parameters of model fitting to the PO -V data in the presence and absence (control) of propofol. Bars represent the mean ± S.E.M. (n = 6). *, p < 0.05, NS, not significant. (D) Simulated PO -V curves with cAMP (50 μΜ) as determined by the model with the same parameter sets used in (B), which closely overlay the experimental data points.