TABLE 2

Actions of JNJ-118 on kinetics of GluA2 coexpressed with wild-type or mutated forms of γ8 and γ2

Summary data for measures of current deactivation and desensitization (τw, deact, τw, des, Iss/Ipeak, and τrec) presented as mean ± S.D. from (n) patches. Also shown are unpaired or paired mean differences (upMD and pMD) with 95% confidence intervals (lower bound, upper bound) and P values from two-sample tests. For TARP effects, Wilcoxon rank-sum tests were used for unpaired comparisons (GluA2+TARP versus GluA2 alone). For the drug effects, Wilcoxon signed-rank tests were used for paired comparisons (JNJ-118 versus corresponding control). For pairwise tests, the P values were adjusted for multiple comparisons within each family of comparisons (for each different measure) using Holm’s sequential Bonferroni correction.

TARP EffectDrug Effect
ControlupMD [95% CI]P value+JNJ-118pMD [95% CI]P value
τw, deact (ms)
 GluA20.41 ± 0.07 (7)0.45 ± 0.13 (7)0.044 [−0.003, 0.17]0.48
 GluA2/γ81.34 ± 0.61 (9)0.93 [0.64, 1.45]0.00190.93 ± 0.47 (9)−0.42 [−0.58, −0.27]0.023
 GluA2/γ8.dm1.12 ± 0.58 (7)0.72 [0.45, 1.36]0.00521.05 ± 0.52 (7)−0.071 [−0.14, 0.007]0.48
 GluA2/γ21.98 ± 1.87 (10)1.57 [0.67, 2.88]0.00121.79 ± 1.50 (10)−0.19 [−0.5, 0.018]0.48
 GluA2/γ2.dm1.34 ± 1.35 (12)0.93 [0.47, 2.35]0.0100.3 ± 0.98 (12)−0.41 [−0.74, −0.26]0.0049
τw, des (ms)
 GluA25.6 ± 0.9 (16)5.0 ± 1.0 (16)−0.54 [−1.19, 0.12]0.30
 GluA2/γ810.6 ± 3.1 (19)5.04 [3.81, 6.75]<0.00017.8 ± 2.1 (19)−2.78 [−4.74, −1.39]<0.0001
 GluA2/γ8.dm10.3 ± 5.1 (16)4.78 [2.88, 8.17]<0.00019.7 ± 3.5 (16)−0.62 [−4.10, 1.88]1.00
 GluA2/γ212.3 ± 5.0 (18)6.75 [4.81, 9.4]<0.000112.3 ± 6.0 (18)0.017 [−3.07, 4.13]1.00
 GluA2/γ2.dm12.0 ± 5.0 (19)6.4 [4.63, 9.47]<0.00015.5 ± 1.7 (19)−6.44 [−9.61, −4.60]<0.0001
Iss/Ipeak (%)
 GluA21.17 ± 1.16 (16)0.90 ± 0.65 (16)−0.27 [−0.68, −0.023]0.65
 GluA2/γ84.51 ± 4.02 (19)3.35 [1.73, 5.53]0.00472.74 ± 1.83 (19)−1.78 [−3.32, -0.78]0.049
 GluA2/γ8.dm4.88 ± 6.23 (16)3.71 [1.55, 8.56]0.0224.30 ± 5.74 (16)−0.58 [−1.49, 0.074]0.53
 GluA2/γ28.09 ± 6.55 (18)6.92 [4.78, 11.6]<0.00017.95 ± 5.89 (18)−0.14 [−1.19, 0.86]0.83
 GluA2/γ2.dm6.98 ± 4.42 (19)5.81 [4.05, 8.11]<0.00013.26 ± 2.31 (19)−3.72 [−5.47, −2.05]0.0047
τrec (ms)
 GluA213.6 ± 2.5 (6)15.6 ± 4.1 (6)2.02 [0.61, 4.37]0.55
 GluA2/γ869.8 ± 14.1 (10)56.2 [47.3, 64.3]0.003262.1 ± 18.5 (10)−7.8 [−14.3, 0.62]0.55
 GluA2/γ8.dm59.7 ± 15.2 (8)46.1 [38.8, 60.4]0.007356.9 ± 29.6 (8)−2.85 [−9.9, 15.3]0.59
 GluA2/γ221.1 ± 7.1 (7)7.47 [2.67, 12.8]0.1317.3 ± 3.4 (7)−3.77 [−9.09, −1.16]0.55
 GluA2/γ2.dm18.8 ± 3.2 (6)5.22 [2.47, 8.38]0.1316.2 ± 2.5 (6)−2.59 [−5.16, −0.25]0.55