Fig. 42.

Modulation of AMPA receptors by PAMs is sensitive to RNA splicing and auxiliary subunits. Left panels: The whole cell current response of homomeric GluA4-flip (A) or GluA4-flop (B) splice isoforms recorded in response to brief application of 10 mM glutamate in the absence or presence of 10 µM of the AMPA receptor PAM BIIB104. Right panels: The current response of GluA4-flip and GluA4-flop receptors in response to prolonged application of 10 mM glutamate in the absence or presence of 10 µM BIIB104 to measure the rate and extent of desensitization. (C) The effect of 1 µM BIIB104 is shown on hippocampal Schaffer collateral to CA1 pyramidal cell EPSCs (upper panel) or on mossy fiber to cerebellar granule cell EPSCs. Reproduced with permission from Ishii et al. (2020). (D) Left panels: Outside-out patch recordings of glutamate-evoked currents from cells expressing AMPA receptors coexpressed with either γ-2 or γ-8 TARPs in the presence (red) and absence (black) of 1 µM JNJ-55511118. Right panels: Outside-out patch recordings of glutamate-evoked currents in patches from hippocampal or cerebellar neurons in the presence (red) and absence (black) of 1 µM JNJ-55511118. Glutamate (10 mM) was applied during the time depicted by the gray bar. Reproduced with permission from Maher et al. (2016).