Table II.
Effect of Binding Site Mutations on AChR Desensitization
| AChR | k O +D | n | θ | |||
|---|---|---|---|---|---|---|
| s−1 | ||||||
| Wild-type, adult | 3.5 | 4 | 45.0 | |||
| Wild-type, fetal* ‡ | 4.6 | 5 | 240.0 | |||
| αW149F | 3.0 | 5 | 0.7 | |||
| αY93F | 1.9 | 4 | 0.7 | |||
| αY93W | 3.4 | 5 | 0.4 | |||
| αY198F | 3.4 | 10 | 10.0 | |||
| αN217K§ | 3.7 | 3 | 19.0 | |||
| αG153S‖ | 3.6 | 6 | 51.0 | |||
| αD200N | 4.4 | 3 | 0.1 | |||
| εD175N | 2.2 | 3 | 0.6 | |||
| εE184I | 4.5 | 4 | 0.8 | |||
| εE184A | 2.2 | 4 | 30.0 |
*
115 mM NaCl in the extracellular solution,
‡
coexpressed with a γ subunit,
§
activated by carbamylcholine, and
‖
activated by tetramethylammonium. Each of the mutations has been shown to influence the rate constants for agonist association, agonist dissociation, and/or channel opening. k O +D is the diliganded AChR desensitization rate constant, computed from (τc P o)−1, n is the number of patches, and θ is the gating equilibrium constant (opening/closing). The mutations have no significant effect on the desensitization rate constant. (142 mM KCl, −100 mV, adult type (ε subunit) activated by ACh, except where noted.