| Site . | Agonist . | f1(s−1) . | b1(s−1) . | E1 . | kon(M−1s−1) . | koff(s−1) . | KdR (μM) . | KdR* (nM) . |
|---|---|---|---|---|---|---|---|---|
| α–ε | ACh | 55.8 | 6,771 | 8.2 × 10−3 | 5.2 × 107 | 3,662 | 70.8 | 5.5 |
| CCh | 32.0 | 7,884 | 4.05 × 10−3 | 1.7 × 107 | 2,236 | 182 | 21 | |
| TMA | 20.1 | 10,615 | 1.9 × 10−3 | 7.8 × 106 | 4,448 | 573 | 195 | |
| Cho | 2.12 | 12,325 | 1.72 × 10−4 | 2.04 × 106 | 5,884 | 2,884 | 10,867 | |
| α–δ | ACh | 24.3 | 5,292 | 4.6 × 10−3 | 3.6 × 107 | 4,631 | 130 | 18.1 |
| CCh | 10.4 | 6,830 | 1.5 × 10−3 | 8.1 × 106 | 3,345 | 413 | 176 | |
| TMA | 7.1 | 8,540 | 8.3 × 10−4 | 4.6 × 106 | 3,559 | 773 | 587 | |
| Cho | 1.1 | 12,950 | 8.5 × 10−5 | 1.6 × 106 | 7,601 | 4,750 | 34,697 | |
| α–δ | Epi | 39.2 | 20,804 | 1.94 × 10−3 | 2.2 × 108 | 1,674 | 7.5 | 2.52 |
| Ebx | 26.9 | 22,427 | 1.2 × 10−3 | 7.4 × 107 | 3,606 | 48.7 | 25.4 | |
| Anx | 6.72 | 23,150 | 2.9 × 10−4 | 3.7 × 107 | 4,273 | 115 | 247 | |
| Aza | 3.11 | 31,211 | 9.9 × 10−5 | 7.7 × 106 | 7,195 | 934 | 6,053 | |
| α–γ | ACh | 377 | 6,658 | 5.6 × 10−2 | 2.9 × 108 | 4,020 | 13.8 | 0.02 |
| CCh | 65.4 | 8,167 | 8.0 × 10−3 | 6.9 × 107 | 7,689 | 111 | 1.25 | |
| TMA | 23.5 | 12,071 | 1.9 × 10−3 | 2.7 × 107 | 8,696 | 322 | 14.9 | |
| Cho | 5.5 | 13,598 | 4.1 × 10−4 | 8.8 × 106 | 10,456 | 1,188 | 230 |
| Site . | Agonist . | f1(s−1) . | b1(s−1) . | E1 . | kon(M−1s−1) . | koff(s−1) . | KdR (μM) . | KdR* (nM) . |
|---|---|---|---|---|---|---|---|---|
| α–ε | ACh | 55.8 | 6,771 | 8.2 × 10−3 | 5.2 × 107 | 3,662 | 70.8 | 5.5 |
| CCh | 32.0 | 7,884 | 4.05 × 10−3 | 1.7 × 107 | 2,236 | 182 | 21 | |
| TMA | 20.1 | 10,615 | 1.9 × 10−3 | 7.8 × 106 | 4,448 | 573 | 195 | |
| Cho | 2.12 | 12,325 | 1.72 × 10−4 | 2.04 × 106 | 5,884 | 2,884 | 10,867 | |
| α–δ | ACh | 24.3 | 5,292 | 4.6 × 10−3 | 3.6 × 107 | 4,631 | 130 | 18.1 |
| CCh | 10.4 | 6,830 | 1.5 × 10−3 | 8.1 × 106 | 3,345 | 413 | 176 | |
| TMA | 7.1 | 8,540 | 8.3 × 10−4 | 4.6 × 106 | 3,559 | 773 | 587 | |
| Cho | 1.1 | 12,950 | 8.5 × 10−5 | 1.6 × 106 | 7,601 | 4,750 | 34,697 | |
| α–δ | Epi | 39.2 | 20,804 | 1.94 × 10−3 | 2.2 × 108 | 1,674 | 7.5 | 2.52 |
| Ebx | 26.9 | 22,427 | 1.2 × 10−3 | 7.4 × 107 | 3,606 | 48.7 | 25.4 | |
| Anx | 6.72 | 23,150 | 2.9 × 10−4 | 3.7 × 107 | 4,273 | 115 | 247 | |
| Aza | 3.11 | 31,211 | 9.9 × 10−5 | 7.7 × 106 | 7,195 | 934 | 6,053 | |
| α–γ | ACh | 377 | 6,658 | 5.6 × 10−2 | 2.9 × 108 | 4,020 | 13.8 | 0.02 |
| CCh | 65.4 | 8,167 | 8.0 × 10−3 | 6.9 × 107 | 7,689 | 111 | 1.25 | |
| TMA | 23.5 | 12,071 | 1.9 × 10−3 | 2.7 × 107 | 8,696 | 322 | 14.9 | |
| Cho | 5.5 | 13,598 | 4.1 × 10−4 | 8.8 × 106 | 10,456 | 1,188 | 230 |
The active-state equilibrium constant was calculated from the activation thermodynamic cycle (Fig. 1 b) assuming microscopic reversibility, KdR* = (KdRE0/E1), where E0 is the unliganded gating equilibrium constant and is equal to 6.6 × 10−7 (ΔG0 = 8.4 kcal/mol) in adult-type and 8.6 × 10−8 (ΔG0 = 9.6 kcal/mol) in fetal-type AChRs. f1 and b1, monoliganded forward and backward gating rate constants (E1 = f1/b1); kon and koff, agonist association and dissociation rate constants to a resting receptor (KdR = koff/kon).