Effect of mutations on modulation of GluR2 by CX614
| Control (τdeact) | Control (τdes) | CX614 (τdeact) | CX614 (τdes) | Fold slowing (τdeact) | Fold slowing (τdes) | % Des + CX614 | |
|---|---|---|---|---|---|---|---|
| WT GluR2(flop) | 0.87 ± 0.06 | 1.21 ± 0.05 | 23.5 ± 1.48 | 207 ± 28.2 | 27 | 171 | 37 ± 4d |
| (21) | (18) | (13) | (10) | ||||
| WT GluR2(flip) | 2.52 ± 0.53 | 4.76 ± 0.29 | 8.91 ± 1.05 | 4 | 48 ± 3 | ||
| (6) | (6) | (6) | |||||
| S497A | 1.86 ± 0.38 | 2.60 ± 0.53 | 31.3 ± 1.68 | 191 ± 28.4 | 17 | 73 | 14 ± 2 |
| (5)a | (5)a | (6)c,# | (6) | ||||
| S497T | 1.03 ± 0.14 | 1.34 ± 0.14 | 0.87 ± 0.06 | 1.32 ± 0.13 | 1 | 1 | 89 ± 3 |
| (9) | (8) | (6)c,* | (5)c,* | ||||
| S729A | 0.93 ± 0.08 | 1.01 ± 0.06 | 19.5 ± 2.21 | 105 ± 10.8 | 21 | 104 | 77 ± 5 |
| (10) | (8) | (6) | (7)c,# | ||||
| S729T | 0.75 ± 0.04 | 0.98 ± 0.02 | 25.4 ± 0.69 | 330 ± 62.4 | 34 | 337 | 10 ± 2 |
| (5) | (4) | (4) | (4) | ||||
| P494A i | 0.37 ± 0.02 | 0.52 ± 0.03 | 0.49 ± 0.06 | 0.64 ± 0.05 | 1 | 1 | 88 ± 4 |
| (21)b | (28)b | (7) | (8) |
Mean ± SEM data for wild-type (WT) and mutant GluR2 receptors. Three functional parameters were measured in the absence and presence of CX614: the time constant of deactivation (τdeact), the time constant of desensitization (τdes), and the ability of CX614 to block desensitization (Des) during a 500 ms pulse of agonist [% des = (1 — ss/pk)(100)]. For example, mutations that impaired modulation by CX614 (i.e., S497T and S729A) desensitized to a greater extent in the presence of the drug.
i, Flop variant was nonfunctional; therefore, flip variant was used.
↵ a Significantly slower than wild-type control kinetics (p ≤ 0.0001).
↵ b Significantly faster than wild-type control kinetics (p ≤ 0.0001).
↵ c Significantly different from wild-type GluR2o kinetics in the presence of CX614. *p ≤ 0.0001; #p ≤ 0.01.
↵ d Control percentage desensitization in the absence of drug is 94 ± 1%.