Table 1. Kinetics of AChR activation by ACh.
| Receptor | k+1 | k−1 | K1 | k+2 | k−2 | K2 | k+2′ | k−2′ | K2′ | p+1 | p−1 | P1 | p+2 | p−2 | P2 | β1 | α1 | Θ1 | β2 | α2 | Θ2 | k+b | k−b | Kb |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| µM | µM | µM | mM | |||||||||||||||||||||
| Wild type | ||||||||||||||||||||||||
| Experiment | 135 | 1,410 | 10 | 134 | 25,000 | 187 | 2150 | 17,200 | 8.0 | 325 | 34,100 | 0.01 | 19,200 | 86,400 | 0.2 | 9,200 | 27,300 | 0.3 | 190,000 | 3,140 | 60 | 150 | 93,000 | 0.6 |
| (6) | (90) | (0.8) | (4) | (18,00) | (14) | (270) | (1,450) | (1.2) | (19) | (2,300) | (0.001) | (800) | (2,600) | (0.001) | (230) | (1,225) | (0.02) | (1,100) | (140) | (2.8) | (1.0) | (714) | (0.06) | |
| Simulateda | 137 | 1,470 | 11 | 130 | 23,000 | 170 | 2,050 | 11,700 | 6.0 | 295 | 33,400 | 0.01 | 13,500 | 51,000 | 0.3 | 10,500 | 29,000 | 0.4 | 320,000 | 6,900 | 46 | 160 | 98,000 | 0.6 |
| (9) | (130) | (1.2) | (8) | (1,000) | (13) | (210) | (1,400) | (0.9) | (28) | (2,500) | (0.001) | (880) | (3,500) | (0.003) | (1,300) | (1,750) | (0.05) | (2,400) | (830) | (5.5) | (2) | (1,200) | (0.01) | |
| Simulatedb | 139 | 1,410 | 10 | 115 | 22,200 | 193 | 1,710 | 16,000 | 9.3 | 310 | 34,000 | 0.01 | 13,700 | 72,800 | 0.2 | 9,700 | 27,800 | 0.3 | 200,000 | 3,180 | 62 | 155 | 9,6000 | 0.6 |
| (10) | (137) | (1.2) | (7) | (1800) | (19) | (190) | (1,640) | (1.5) | (26) | (2,330) | (0.001) | (940) | (3,300) | (0.001) | (1,150) | (1,230) | (0.04) | (18,100) | (250) | (7.8) | (2.0) | (1,066) | (0.01) | |
| αG153S | ||||||||||||||||||||||||
| Experiment | 365 | 844 | 2.3 | 300 | 2,450 | 8.0 | 12,100 | 26,000 | 2.1 | 460 | 4,330 | 0.1 | 30,500 | 75,900 | 0.4 | 4,600 | 47,200 | 0.3 | 240,000 | 3,600 | 67 | 176 | 120,000 | 0.7 |
| (27) | (110) | (0.3) | (14) | (190) | (0.7) | (950) | (1,800) | (0.2) | (58) | (390) | (0.001) | (1,600) | (3,000) | (0.03) | (344) | (5,300) | (0.01) | (23,400) | (340) | (6) | (3) | (945) | (0.01) | |
| Simulateda | 357 | 719 | 2.0 | 268 | 2,240 | 8.3 | 10,601 | 11,400 | 1.2 | 450 | 4,540 | 0.1 | 21,700 | 28,200 | 0.7 | 5,550 | 48,000 | 0.1 | 440,000 | 13,500 | 33 | 190 | 120,000 | 0.6 |
| (36) | (117) | (0.1) | (21) | (210) | (1) | (700) | (1,280) | (0.1) | (58) | (360) | (0.01) | (1,000) | (2,900) | (0.09) | (480) | (600) | (0.01) | (2,700) | (2,100) | (2) | (6) | (3,000) | (0.01) | |
| Simulatedb | 374 | 860 | 2.3 | 272 | 2,100 | 7.8 | 9,200 | 24,100 | 2.6 | 560 | 4,410 | 0.13 | 22,000 | 58,200 | 0.4 | 4,900 | 47,700 | 0.1 | 250,000 | 3,700 | 67 | 192 | 110,000 | 0.6 |
| (37) | (150) | (0.5) | (24) | (166) | (0.9) | (630) | (1,616) | (0.2) | (70) | (340) | (0.02) | (1,100) | (2,900) | (0.03) | (360) | (3,400) | (0.01) | (20,600) | (340) | (8.3) | (5) | (2,700) | (0.01) |
Rate constants were estimated from fitting Scheme 1 to global dwell time sequences obtained over a range of ACh concentrations, with errors computed by the MIL program in parenthesis (Materials and methods). Units of the rate constants are µM−1s−1 for association rate constants, and s−1 for all others. The channel gating equilibrium constants (Θn) are βn/αn, and the dissociation constants (K) are k−/k+.
a
Results from analysis of simulated data with experimental fitted parameters as the input.
b
Results from analysis of simulated data with the experimental fitted parameters, except with slower channel opening and closing rate constants (wild type: 125,000/2,100; αG153S: 150,000/2,400) as the input.