Extended Data Fig. 5: TARP γ2 increases the Ca2+ permeability of missense mutations.
From: GluA2-containing AMPA receptors form a continuum of Ca2+-permeable channels
a. The Ca2+ reversal potential shift with the GluA2 missense mutations (D611N in green, R607G in light blue and R607E in dark blue) in the absence and presence of TARP γ2. b. The Na+-relative Ca2+ permeability of GluA1+ GluA2 missense mutations (D611N in green, R607G in light blue and R607E in dark blue) in the absence and presence of TARP γ2. Two-sided two-way between-subject ANOVA was performed upon the dataset, decomposing with Tukey’s HSD post hoc analysis respectively. #: p < 0.05; ***: p < 0.001. c. IV plots of GluA2-containing AMPARs mutated at the pore region (D611N) and the pore selectivity filter (R607G and R607E). d. GV plots obtained from IV curves above (c). A1 + A2D611N channels exhibit a linear GV relationship while A1 + A2R607G and A1 + A2R607E GV curves show block by internal spermine (A1 + A2R607G Kd(0 mV) = 34 ± 6.5 μM n = 4 and A1 + A2R607E Kd(0 mV) = 4.4 ± 0.9 μM n = 5). Open circles show average normalized response, colored shading show se.m., and the solid red line corresponds to the fit of a single permeant blocker model. e. IV plots of different A1/A2γ2 AMPARs mutated at the +4 site (D611N) and selectivity filter (R607G and R607E). f. GV plots obtained from IV curves above (e). A1/A2γ2D611N channels show a linear GV relationship while A1/A2γ2R607G and A1/A2γ2R607E GV curves show sensitivity to block by internal spermine (A1/A2γ2R607G Kd(0 mV) = 38.2 ± 11.7 μM n = 5 and A1/A2γ2R607E Kd(0 mV) = 14.5 ± 3.4 μM n = 7). Open circles show average normalized response, colored shading show s.e.m., and the solid redline denotes fits using a single permeant blocker model.
