TABLE 1

Kinetic parameters for hERG channel gating in control and presented of AMD at 22°C and 37°C

Voltage-dependent rates are expressed as k(v) = k0 exp (k1V), where k(v) stands for the transitional rate at a designated membrane potential V (in millivolts) at 22°C. Transitions with negligible transitioned rates (i.e., zero) are not indicated here for the sake of simplicity. For the electronic charge displacement during activation, please also refer to the single unit of voltage sensors movement in previous hERG models (Johnson et al., 1999; Bett et al., 2011). The values are based on the root template (22°C), and each transition of the conditions at 37°C is given. The changes in voltage dependence of activation (C1↔C2↔C3↔C4) by AMD are based on the experiments in Figs. 1 and 3. The increase of silent route for entry to and recovery from inactivation by AMD (IO2→IO1, IO1→I5) is based on the experiments in Fig. 5. The slowing of transitions into inactivation (C→I and O→I) at higher temperatures, and the increase of voltage dependency of inactivation (C→I and O→I) when in the presence of AMD are based on the experiments in Figs. 13 and 5. The major changes made by AMD are shown in bold.

ControlAmiodarone
k0 (ms−1)k1 (mV−1)k0 (ms−1)k1 (mV−1)
C1C22.96(22°C) vs. 5.437867(37°C)0.146C1AC2A2.96(22°C) vs. 5.437867(37°C)0.155(22°C) vs. 0.148(37°C)
C2C30.71821(22°C) vs. 0.944112(37°C)0.049(22°C) vs. 0.0265(37°C)C2AC3A0.71821(22°C) vs. 0.944112(37°C)0.059(22°C) vs. 0.009(37°C)
C3C40.55821(22°C) vs. 1.698739(37°C)0.002(22°C) vs. 0.001(37°C)C3AC4A0.55821(22°C) vs. 1.698739(37°C)0.005(22°C) vs. 0.001(37°C)
C4C50.035321(22°C) vs. 0.348799(37°C)0.001C4AC5A0.035321(22°C) vs. 0.348799(37°C)0.001
C5O11.05E–5(22°C) vs. 4.7E–5(37°C)0.001C5AO1A1.05E–5(22°C) vs. 4.96E–5(37°C)0.001
O1O20.02545(22°C) vs. 0.029361 (37°C)0.00071547O1AO2A0.028630.00071547
C2C10.00001(22°C) vs. 0.000015(37°C)−0.07966C2AC1A0.00001(22°C) vs. 0.000033(37°C)−0.07966
C3C20.6(22°C) vs. 0.889337(37°C)−0.00166C3AC2A0.6(22°C) vs. 1.957876(37°C)−0.00166
C4C31.2(22°C) vs. 2.204541(37°C)−0.00166C4AC3A1.2(22°C) vs. 3.142763 (37°C)−0.00166
C5C41.8(22°C) vs. 3.989752(37°C)−0.04366C5AC4A1.8(22°C) vs. 3.989752(37°C)−0.04366
O1C50.00055(22°C) vs. 0.000602(37°C)−0.04158O1AC5A0.00055(22°C) vs. 0.000802(37°C)−0.04158
O2O10.12(22°C) vs. 0.424824(37°C)−0.08158O2AO1A0.1651(22°C) vs. 0.24445(37°C)−0.08158
C4C31.2(22°C) vs. 2.2045401(37°C)−0.00166C4AC3A1.2(22°C) vs. 3.142763(37°C)−0.00166
C3C20.6(22°C) vs. 0.889337(37°C)−0.00166C3AC2A0.6 vs. 1.957876(37°C)−0.00166
C2C10.00001(22°C) vs. 0.000015(37°C)−0.07966C2AC1A0.00001 vs. 0.000033(37°C)−0.07966
I1I20.011(22°C) vs. 0.020208(37°C)0.146I1AI2A0.011 vs. 0.01446(37°C)0.155(22°C) vs. 0.148(37°C)
I2I30.011(22°C) vs. 0.01446(37°C)0.049(22°C) vs. 0.0265(37°C)I2AI3A0.011 vs. 0.020208(37°C)0.059(22°C) vs. 0.009(37°C)
I3I40.00011(22°C) vs. 0.000335(37°C)0.002(22°C) vs. 0.001(37°C)I3AI4A0.00011 vs. 0.000335(37°C)0.005(22°C) vs. 0.001(37°C)
I4I50.0128(22°C) vs. 0.018973(37°C)0.001I4AI5A0.01392 vs. 0.020633(37°C)0.001
I5IO10.068188(22°C) vs. 0.078668(37°C)0.001I5AIO1A0.07127 vs. 0.130931(37°C)0.001
IO1IO20.073695(22°C) vs. 0.085021(37°C)0.00071547IO1AIO2A0.11260.00071547
IO2IO10.83054(22°C) vs. 2.448496 (37°C)−0.08158IO2AIO1A1.265(22°C) vs. 3.74082(37°C)−0.08158
IO1I50.069357(22°C) vs. 0.129264(37°C)−0.04158IO1AI5A0.079857(22°C) vs. 0.173907(37°C)−0.04158
I5I40.061484(22°C) vs. 0.09195(37°C)−0.04366I5AI4A0.065484(22°C) vs. 0.09195(37°C)−0.04366
I4I30.000042(22°C) vs. 0.000059(37°C)−0.00166I4AI3A0.00035(22°C) vs. 0.000524(37°C)−0.00166
I3I22.0e–9(22°C) vs. 2.96446E–9(37°C)−0.00166I3AI2A2.0E–9(22°C) vs. 6.526254E–9(37°C)−0.00166
I2I12.0e–9(22°C) vs. 2.96446E–9(37°C)−0.07966I2AI1A2.0E–9(22°C) vs. 6.526254E–9(37°C)−0.07966
C4I40.0232(22°C) vs. 0.0106(37°C)0.039942C4AI4A0.03215(22°C) vs. 0.0111(37°C)0.0451
C5I50.0369(22°C) vs. 0.025(37°C)0.039942C5AI5A0.0479(22°C) vs. 0.0285(37°C)0.0451
O1IO10.492(22°C) vs. 0.055(37°C)0.039942O1AIO1A0.492(22°C) vs. 0.055(37°C)0.0451
O2IO20.8(22°C) vs. 0.2(37°C)0.039942O2AIO2A0.8(22°C) vs. 0.2(37°C)0.0451
I4C43.80E–5(22°C) vs. 1.70889e–5(37°C)−0.048(22°C) vs. −0.075(37°C)I4AC4A3.75E–5(22°C) vs. 4.9295E–5(37°C)−0.048(22°C) vs. −0.075(37°C)
I5C53.80E–5(22°C) vs. 1.70889e–5(37°C)−0.048(22°C) vs. −0.075(37°C)I5AC5A3.75E–5(22°C) vs. 4.9295E–5(37°C)−0.048(22°C) vs. −0.075(37°C)
IO1O13.80E–5(22°C) vs. 1.70889E–5(37°C)−0.048(22°C) vs. −0.075(37°C)IO1AO1A3.75E–5(22°C) vs. 4.9295E–5(37°C)−0.048(22°C) vs. −0.075(37°C)
IO2O20.0001056(22°C) vs. 0.000139(37°C)−0.048(22°C) vs. −0.075(37°C)IO2AO2A0.0001188(22°C) vs. 0.0001562(37°C)−0.048(22°C) vs. −0.075(37°C)