Table 2. Kinetics of AChR activation by CCh.
| 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 | 1,280 | 6,520 | 5.1 | 10.5 | 13,000 | 1,240 | 290 | 16,980 | 58 | 75 | 79,800 | 0.001 | 1,500 | 75,300 | 0.02 | 8,200 | 6,370 | 1.3 | 310,000 | 6,200 | 50 | 280 | 360,000 | 1.3 |
| (230) | (1,040) | (0.7) | (0.8) | (2,100) | (286) | (55) | (6900) | (26) | (20) | (12,000) | (0.0001) | (400) | (4,600) | (0.002) | (4,700) | (290) | (0.7) | (1,100) | (530) | (4) | (10) | (5,300) | (0.03) | |
| Simulateda | 1,250 | 5,500 | 4.4 | 8.7 | 11,000 | 1,270 | 345 | 21,000 | 61 | 75 | 75,600 | 0.001 | 1,400 | 69,000 | 0.02 | 8,200 | 6,290 | 1.3 | 330,000 | 10,700 | 31 | 320 | 330,000 | 0.6 |
| (270) | (640) | (1) | (0.9) | (1,300) | (200) | (58) | (3,300) | (14) | (11) | (6,500) | (0.0001) | (190) | (5,200) | (0.002) | (1,560) | (220) | (0.2) | (7,200) | (700) | (2.1) | (9.4) | (3,500) | (0.01) | |
| Simulatedb | 1700 | 7,200 | 4.2 | 10.1 | 14,300 | 1,410 | 270 | 5,210 | 19 | 40 | 96,200 | 0.001 | 1,200 | 39,500 | 0.03 | 22,100 | 6,640 | 3.3 | 310,000 | 6,700 | 46 | 310 | 330,000 | 1.1 |
| (340) | (600) | (0.9) | (0.8) | (1200) | (160) | (31) | (780) | (3.6) | (5) | (70) | (0.0002) | (140) | (4,700) | (0.003) | (4,200) | (320) | (0.7) | (10,400) | (500) | (3.8) | (7) | (3,000) | (0.01) | |
| αG153S | ||||||||||||||||||||||||
| Experiment | 190 | 1,040 | 5.5 | 170 | 17,200 | 100 | 140 | 4,600 | 33 | 370 | 24,000 | 0.015 | 6,100 | 124,000 | 0.05 | 5,100 | 11,400 | 0.45 | 330,000 | 6,400 | 50 | 470 | 440,000 | 0.9 |
| (20) | (140) | (4) | (5) | (2,500) | (10) | (30) | (1,100) | (10) | (30) | (2,300) | (0.0001) | (400) | (11,000) | (0.002) | (650) | (600) | (0.07) | (1,100) | (900) | (8.9) | (3) | (8,700) | (0.01) | |
| Simulateda | 250 | 1,380 | 5.6 | 175 | 14,700 | 84 | 86 | 1,400 | 16 | 345 | 26,600 | 0.01 | 4500 | 66,700 | 0.07 | 5,500 | 11600 | 0.5 | 340,000 | 9,910 | 34 | 490 | 360,000 | 0.7 |
| (12) | (50) | (3.4) | (6) | (500) | (4) | (26) | (46) | (7) | (34) | (2,800) | (0.001) | (940) | (4,600) | (0.01) | (740) | (580) | (0.07) | (7,800) | (2,100) | (1.7) | (11) | (3,000) | (0.01) | |
| Simulatedb | 250 | 1,450 | 5.8 | 170 | 15,000 | 89 | 70 | 1,950 | 28 | 370 | 25,700 | 0.01 | 3,370 | 73,700 | 0.05 | 5,200 | 9,980 | 0.5 | 320,000 | 6,650 | 48 | 490 | 370,000 | 0.7 |
| (13) | (60) | (0.5) | (9) | (1,800) | (6.6) | (23) | (720) | (13) | (38) | (2,800) | (0.02) | (800) | (6,400) | (0.03) | (700) | (450) | (0.01) | (1,400) | (520) | (3.7) | (5) | (2,700) | (0.01) |
Rate constants were estimated from fitting Scheme 1 to global dwell time sequences obtained over a range of CCh 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: 100,000/1,900; αG153S: 130,000/2,500).