TABLE 2

IC50 values for PMP, CP, and GYKI at WT and mutant GluA2 The IC50 values were determined by the nonlinear fitting of composite concentration-inhibition data from at least three independent experiments (TEVC or Ca2+) (see Materials and Methods). Numbers in brackets denote the 95% confidence interval for the fitted IC50. *P < 0.05; **P < 0.01; ***P < 0.001 significantly different from blac-GluA2 (ANOVA). To maintain an overall familywise α of 5%, for each dependent variable separate ANOVA with Dunnett’s post hoc test were run at α = 0.05/dv, where dv is the number of dependent variables. N.D. not determined.

ConstructPMPCPGYKI
[Ca2+]iTEVC[Ca2+]iTEVC[Ca2+]iTEVC
GluA229 [28–29]***4.3 [4.2–4.4]***2.5 [2.5–2.6]**2.5 [2.4–2.6]230 [230–230]***20 [19–21]
blac-GluA216 [15–18]2.4 [2.3–2.5]1.1 [1.0–1.2]2.4 [2.3–2.6]120 [110–120]25 [25–26]
K511G>100***9.6 [9.3–9.9]***9.3 [7.0–12]***3.3 [3.1–3.4]>2000***62 [49–78]***
P512G9.8 [8.4–11]*4.4 [4.3–4.5]***5.5 [5.0–6.0]***7.5 [7.2–7.8]***140 [100–180]79 [75–84]***
V514G>100***29 [26–31]***>100***10 [9.6–10]***>2000***620 [450–850]***
V514A>100***4.7 [4.4–4.9]***27 [23–31]***3.3 [3.1–3.6]>2000***11 [10–12]***
V514D19 [14–26]11 [11–11]***6.0 [5.8–6.3]***4.0 [3.8–4.3]>2000***69 [66–73]***
V514W87 [71–110]***2.3 [2.3–2.4]4.2 [3.7–4.7]***0.9 [0.9–1.0]***>2000***18 [18–19]
F515G4.1 [3.7–4.5]***1.6 [1.6–1.6]***0.7 [0.7–0.8]1.6 [1.6–1.7]20 [19–21]***7.9 [7.7–8.1]***
F515A4.5 [3.7–5.6]***N.D.0.4 [0.4–0.4]**N.D.49 [42–57]***N.D.
S516G23 [19–27]N.D.3.5 [3.3–3.8]***N.D.670 [520–860]***N.D.
F517G1.0 [1.0–1.1]***N.D.0.3 [0.3–0.3]***N.D.13 [12 to 13]***N.D.
F517A4.9 [4.6–5.2]***N.D.2.4 [2.1–2.6]N.D.53 [47–58]***N.D.
L518A2.9 [2.5–3.2]***3.8 [3.7–3.9]***0.8 [0.8–0.8]1.9 [1.8–1.9]28 [27–30]***28 [27–29]
D519G10 [9.2–11]**N.D.3.7 [3.4–4.0]***N.D.19 [17–20]***N.D.
D519N24 [17–34]3.3 [3.2–3.5]***61 [18–210]***7.4 [7.0–7.8]***55 [47–63]***8.1 [7.7–8.5]***
A522G17 [14–20]N.D.1.7 [1.6–1.8]N.D.310 [280–350]***N.D.
A522S16 [14–18]N.D.2.4 [2.2–2.7]N.D.510 [400–650]***N.D.
Y523G12 [10–14]N.D.1.2 [1.2–1.3]N.D.91 [77–1107]N.D.
Y523P18 [12–27]N.D.3.1 [2.8–3.4]**N.D.370 [320–430]***N.D.
Y523R15 [13–17]N.D.1.8 [1.6–1.9]N.D.84 [76–93]*N.D.
E524G9.5 [8.7–10]***N.D.0.5 [0.5–0.5]*N.D.48 [43–52]***N.D.
E524D23 [19–27]2.0 [1.9–2.1]***5.0 [3.9–6.4]***1.6 [1.5–1.6]140 [110–180]14 [14–15]**
M527G8.9 [7.9–10]**N.D.0.5 [0.4–0.6]N.D.120 [100–140]
S615A>100***2.2 [2.1–2.3]3.5 [3.3–3.7]*0.2 [0.2–0.2]***>2000***31 [14–66]
Y616FN.D.0.9 [0.5–1.7]***N.D.1.8 [1.6–1.9]N.D.26 [15–46]
F623A>100***>100***12 [7.2–21]***51 [4.4–590]***100 [88–120]87 [35–210]***
E782G12 [11–13]N.D.1.1 [1.1–1.2]N.D.100 [97–110]N.D.
K783G27 [19–39]**N.D.2.7 [2.6–2.8]*N.D.170 [160–180]**N.D.
T784G8.5 [7.3–9.8]***7.9 [7.6–8.2]***1.1 [1.0–1.2]2.5 [2.5–2.5]23 [21–25]***22 [22–23]
S785G10 [9.0–11]**3.5 [3.4–3.7]***1.1 [1.0–1.2]1.7 [1.6–1.7]39 [36–42]***12 [12–12]***
A786G1.4 [1.3–1.6]***2.7 [2.6–2.7]**0.6 [0.5–0.6]3.1 [3.0–3.2]18 [17–19]***11 [11–12]***
L787A37 [18–74]***N.D.7.1 [6.6–7.6]***N.D.630 [500–780]***N.D.
S788G16 [14–18]N.D.0.6 [0.6–0.6]N.D.92 [77–110]N.D.
L789G4.8 [4.3–5.4]***N.D.0.4 [0.3–0.4]***N.D.61 [51–73]***N.D.
S790G9.9 [5.4–18]*N.D.1.5 [1.4–1.7]N.D.140 [100–180]N.D.
N791G8.7 [6.4–12]***N.D.15 [9.2–24]***N.D.350 [300–420]***N.D.
N791A>100***1.5 [1.5–1.6]***>100***11 [10–13]***>2000***21 [21–22]
N791F3.7 [3.5–3.8]***N.D.1.9 [1.9–2.0]N.D.22 [20–23]***N.D.
N791L14 [13–15]N.D.25 [19–33]***N.D.66 [62–69]***N.D.
V792I14 [12–16]1.2 [1.2–1.3]***13 [9.2–17]***2.1 [2.0–2.2]170 [140–200]*11 [10–11]***
A793G12 [8.9–17]N.D.1.1 [1.0–1.2]N.D.180 [150–220]***N.D.
A793D27 [18–41]**N.D.170 [8.6–3500]***N.D.190 [170–200]***N.D.
A793H15 [12–18]N.D.3.7 [3.0–4.5]***N.D.110 [110–120]N.D.
G794D37 [30–46]***5.5 [5.4–5.7]***11 [8.4–14]***2.8 [2.7–2.9]280 [250–310]***40 [39–41]*
V795G15 [10–21]N.D.1.1 [0.9–1.2]N.D.87 [74–100]N.D.