TABLE 2.
Modulation of AMPA receptor properties by auxiliary subunits
Values at 2–3 significant figures are from the text or tables; when values are not reported, measurements were made from figures.
| Receptor a | Subunit b | Mean γ c | EC50,SS d (EC50,PEAK) e | τ-Deactivate f | τ-Desensitize f | τ-Recovery g |
Steady State/Peak
Current Ratio |
|---|---|---|---|---|---|---|---|
| pS | μM (mM) | ms | ms | ms | |||
| GluA1 | – | 16–20 | 15-37 (0.9–1.6) | 0.5–2.9 | 2.3–4.1 | 83–160 | 0.003–0.019 |
| GluA1 | γ−2 | ↑ 27 4,6 | ↓ 5–6 (0.27–0.46) 2,6,8,10,11 | ↑ 1.4–3.3 2,8,10,15,18,28,31 | ↑ 3.9–7.4 2,4,8,10,28,31 | ↓ 55–170 6,15 | ↑ 0.02–0.09 2,8,9,28 |
| GluA1 | γ−3 | ↑ 274 | ↓ 5.3 11 | ↑ 2.2–3.0 15,28,31 | ↑ 5.0–5.5 2,28,31 | – | ↑ 0.02 9,28 |
| GluA1 | γ−4 | 26–32 3 | ↓ 20 11 | ↑ 2.4–12 3,15,28,31 | ↑ 5.2–9.6 3,28,31 | – | ↑ 0.052 28 |
| GluA1 | γ−5 | ↑ 44 3 | ↑ 100 21 | 1.3 10 | 2.3–4 3,10 | – | – |
| GluA1 | γ−7 | – | 20 10 | ↑ 1.8 10 | ↑ 6 10 | – | – |
| GluA1 | γ−8 | – | ↓ 17 11 | ↑ 2.5–7.7 15,19,20,28,31 | ↑ 5.9–12 19,20,23,28,31 | ↓ 65–150 15,19 | ↑ 0.047–0.17 19,23,28 |
| GluA1 | GSG1L | ↓ 11 1 | – | – | – | – | – |
| GluA1 | CNIH2 | ↑ 30 2 | ↓ 9.4 (0.92) 2 | ↑ 4.0–9 2,15,20 | ↑ 5.5–13 2,20 | ↓ 135 15 | 0.067 2 |
| GluA1 | CNIH3 | ↑ 28 2 | – | ↑ 3.3 2 | ↑ 5.0 2 | – | 0.041 2 |
| GluA1 | CKAMP39 | – | ↓ 8.0 7 | 1.9 7 | 3.0 7 | ↑ 950 7 | 0.008 7 |
| GluA1 | CKAMP44 | – | ↓ 3.6 7 | – | 3.3 23 | – | ↓ 0.008 23 |
| GluA1 | CKAMP52 | – | ↓ 4.8 7 | 1.9 7 | 3.8 7 | 96 7 | ↑ 0.016 7 |
| GluA1 | CKAMP59 | – | – | 1.9 7 | 3.7–4.5 7,12 | 95–120 7,12 | 0.007 7 |
| GluA1 | SynDIG4 | – | – | ↑ 4.8 19 | ↑ 5.9 19 | 206 19 | 0.021 19 |
| GluA2 | – | 5.1 | 50 | 1.0 | 10 | – | 0.01–0.12 |
| GluA2 | γ−2 | 3.8 27 | – | ↑ 2.5–3.7 21,27 | 10–13 21,27 | – | ↑ 0.25–0.53 9,21,27 |
| GluA2 | γ−3 | – | – | – | – | – | ↑ 0.03 9 |
| GluA2 | γ−5 | 6.5 3 | ↑ 300 21 | 1.8 21 | ↓ 7 21 | – | ↓ 0.005–0.02 9,21 |
| GluA2 | γ−8 | – | – | – | ↑ 17 27 | – | ↑ 0.30 27 |
| GluA2 | GSG1L | – | – | – | 12 27 | – | 0.01427 |
| GluA2Q | – | 19–22 | 28–170 | 0.55–1.8 | 4.8–9.2 | 15–22 | 0.018–0.05 |
| GluA2Q | γ−2 | ↑ 30–31 2,3,27 | – | ↑ 0.67–5.0 22,24,27,30 | ↑ 10–45 2,22,24–26,30 | 13–22 22,30 | ↑ 0.07–0.27 2,8,22,24-26,30 |
| GluA2Q | γ−3 | – | – | – | ↑ 12 30 | 22 30 | ↑ 0.08 30 |
| GluA2Q | γ−4 | – | – | – | ↑ 13 30 | ↑ 67 30 | ↑ 0.05 30 |
| GluA2Q | γ−5 | ↑ 26 3 | 160 21 | – | 7.6 3 | 19 3 | – |
| GluA2Q | γ−7 | – | – | – | ↑ 16 24 | – | – |
| GluA2Q | γ−8 | ↑ 35 27 | – | – | ↑ 11–25 26,30 | ↑ 78 30 | ↑ 0.075–0.25 26,30 |
| GluA2Q | GSG1L | ↓ 12–13 1,27 | – | ↑ 5.9 13 | 9–11 5,13,27 | ↑ 160–200 5,13 | 0.032 13 |
| GluA2Q | CNIH2 | ↑ 29 2 | – | – | ↑ 12 2 | – | ↑0.089 2 |
| GluA2Q | CNIH3 | ↑ 33 2 | – | ↑ 12 2 | ↑ 26–36 2,25 | – | ↑0.11–0.13 2,25 |
| GluA2Q | CKAMP39 | – | ↓ 11 7 | 1.6 7 | ↑ 4.4 7 | ↑ 78 7 | ↑0.005 7 |
| GluA2Q | CKAMP44 | – | ↓ 11 7 | – | – | ↑ 130 23 | – |
| GluA2Q | CKAMP52 | – | ↓ 1.7 7 | ↑ 2.1 7 | 7.8 7 | 16 7 | ↑ 0.050 7 |
| GluA2Q | CKAMP59 | – | – | 1.7 7 | 7.7 7 | 25 7 | 0.020 7 |
| GluA4 | – | 20 | (0.81) | 0.6 | 3.5 | – | 0.014 |
| GluA4 | γ−2 | ↑ 31 3 | ↓ (0.39) 33 | 1.7 29 | ↑ 5.7 3 | – | ↑ 0.078 9 |
| GluA4 | γ−3 | ↑ 33 3 | – | – | ↑5.4 3 | – | – |
| GluA4 | γ−4 | ↑ 34 3 | ↓ (0.65) 33 | 9 3 | ↑12 3 | – | – |
| GluA4 | γ−5 | ↑ 36 3 | – | 2 3 | 3.0 3 | – | 0.014 21 |
| GluA4 | γ−7 | ↑ 33 3 | – | – | 3.3 3 | – | 0.056 21 |
| GluA4 | γ−8 | ↑ 37 3 | – | 1.6 29 | ↑ 7.8 3 | – | – |
| GluA1/2 | – | 3.0–4.4 | 40 | 0.8–4.5 | 4.8–6.3 | 58–87 | 0.020–0.046 |
| GluA1/2 | γ−2 | ↑ 6.2–7.1 2,17 | – | ↑ 3.4 14 | ↑ 6–7.7 2,14 | – | ↑ 0.16–0.20 2,9 |
| GluA1/2 | γ−5 | – | 80 21 | – | – | – | 0.018 9 |
| GluA1/2 | γ−8 | ↑ 6.4 17 | – | ↑ 1.7–9.5 19,29 | ↑ 11–33 19,32,34 | ↑ 110–160 19,32,34 | ↑ 0.085–0.18 19,32 |
| GluA1/2 | GSG1L | – | – | ↑ 2.5 34 | 8.1 34 | ↑ 580 34 | – |
| GluA1/2 | CNIH2 | 5.6 2 | – | ↑ 8.3 14 | ↑ 14 2,14,34 | 69–75 14,34 | ↑ 0.15–0.25 2,14,34 |
| GluA1/2 | CNIH3 | 5.1 2 | – | ↑ 1.3–7 2,14 | ↑ 11–22 2,14 | 45 14 | ↑ 0.13–0.20 2,14 |
| GluA1/2 | CKAMP52 | – | – | ↑ 5.8 16 | ↑ 6.0 16 | ↑ 110 16 | ↑ 0.12 16 |
| GluA1/2 | SynDIG4 | – | – | ↑ 5.3 19 | 5.8 19 | 62 19 | 0.021 19 |
| GluA2/4 | – | – | – | 0.71 | 0.92 | 39 | 0.01 |
| GluA2/4 | CNIH2 | – | – | ↑ 2.6 14 | ↑ 3.4 14 | 48 14 | ↑ 0.10 14 |
| GluA2/4 | CNIH3 | – | – | ↑ 2.6 14 | ↑ 3.5 14 | 45 14 | ↑ 0.10 14 |
a All receptors are rat flip splice isoforms, except GluA2/4 that was GluA2-flop/GluA4-flop. See Turetsky et al. (2005), Kato et al. (2007), Soto et al. (2009), Tomita et al. (2006), Dawe et al. (2016) and Ishii et al. (2020) for data on the effects of auxiliary subunits on different AMPA receptor splice isoforms. GluA2Q indicates cDNA for the unedited GluA2 with Gln at the Q/R/N site. Some authors report the median [e.g., Farrow et al. (2015)]. There is minimal information available for GluA3 with γ−5 increasing the conductance and the steady state to peak current ratio (Soto et al., 2009; Turetsky et al., 2005).
b Data for receptors in the absence of auxiliary subunits are only from the references providing data about auxiliary subunit for that receptor combination. Time constants that were considerably slower than the range of others were omitted under the assumption that solution exchange was insufficient to resolve the response time course accurately. For TARPs, some variability in reported values reflects different stoichiometry (Miguez-Cabello et al., 2020). Values are mean range; some papers reported median values.
c Weighted mean chord conductance was determined from variance analysis.
d EC50 was determined from the steady-state (SS) response from oocytes or transfected HEK cells; Farrow et al. (2015), Kato et al. (2008), and Priel et al. (2005) determined EC50 in the presence of cyclothiazide; GluA1-L497Y abolished effects of γ−2 on EC50h.
e EC50 was determined from the peak response to rapid glutamate application in HEK cells or macropatches from Xenopus oocytes.
f When more than one exponential described the deactivation or desensitization time course, the weighted mean time constants are given.
g The time course of recovery from desensitization was estimated from a single exponential, although it can be more complex (Bowie and Lange, 2002; Robert and Howe, 2003). When multiple exponential components were fitted to the time course, the weighted mean time constant is given. See Lomeli et al. (1994) for R/G RNA editing control of the rate of recovery from desensitization.
↑ and ↓ indicate that the measured parameter was reported to be significantly greater than or less than that for the receptor lacking the auxiliary subunit and was used when either statistical tests were reported or reported values did not have overlapping confidence intervals. ND indicates data were not compared with control. When conflicting results were reported, no direction is shown.
(Table 2 legend, cont.) 1 McGee et al. (2015), 2 Coombs et al. (2012), 3 Soto et al. (2009), 4 Soto et al. (2014), 5 Shanks et al. (2012), 6 Coombs et al. (2017), 7 Farrow et al. (2015), 8 Priel et al. (2005), 9 Turetsky et al. (2005), 10 Kato et al. (2007), 11 Kott et al. (2007), 12 Schmitz et al. (2017), 13 Twomey et al. (2017b), 14 (Schwenk et al., 2009), 15 Gill et al. (2012), 16 Klaassen et al. (2016), 17 Kristensen et al. (2011), GluA1 contains mutations S831A and S845A, 18 Tomita et al. (2006), 19 Matt et al. (2018), 20 Kato et al. (2010), 21 Kato et al. (2008), 22 Twomey et al. (2016), some measures from tandem fusion protein of GluA2Q and γ−2, 23 Khodosevich et al. (2014), 24 Dawe et al. (2016), 25 Hawken et al. (2017), 26 Riva et al. (2017), 27 Coombs et al. (2019), 28 Cho et al. (2007), 29 Ishii et al. (2020), 30 Cais et al. (2014), 31 Milstein et al. (2007), 32 Herguedas et al. (2019), 33 Pierce and Niu (2019), 34 Schwenk et al. (2012).