Table 1. Gating rate constants for AChR mutants.
Construct | Predicted opening rate constant, β2 | Predicted closing rate constant, α2 |
---|---|---|
Slow-closing | ||
δS268G | 43,772 | 1,897 |
δS268C | 78,566 | 363 |
δS268T | 93,580 | 369 |
δS268V | 107,468 | 131 |
δS268N | 138,751 | 107 |
δL265′T | 44,349 | 88 |
δL265′T+αD97C | 191,457 | 91 |
δL265′T+αD97E | 884,093 | 86 |
δL265′T+αD97Q | 2.163E6 | 85 |
δL265′T+αD97A | 4.972E6 | 72 |
Fast-opening | ||
αD97N | 96,630 | 1,617 |
αD97C | 191,457 | 1,476 |
αD97M | 301,068 | 1,532 |
αD97Y | 503,342 | 1,354 |
αD97H | 663,430 | 1,317 |
αD97E | 883,372 | 1,410 |
αD97F | 990,819 | 1,244 |
αD97Q | 2,165E6 | 1,370 |
αD97R | 3.948E6 | 1,123 |
αD97A | 4.972E6 | 1,168 |
All values are s-1 and pertain to diliganded AChRs activated by ACh. The predicted opening and closing rate constants are calculated from the corresponding values measured for choline and using Eq 1 (see Materials and Methods). The calculated opening and closing rate constants for WT AChRs activated by ACh are 44,349 s-1 and 1,583 s-1, respectively, and are similar to the experimentally determined values of ≈48,000 s-1 and ≈1,700 s-1, respectively. The double-mutant constructs in the slow-closing series also open rapidly, but it is mainly their slow α-values that cause k* to approach zero and, hence, drive τb towards σ-1 (Eq. 3).