Two families of TARP isoforms that have distinct effects on the kinetic properties of AMPA receptors and synaptic currents.

Transmembrane AMPA receptor regulatory proteins are auxiliary AMPA receptor subunits that regulate both the trafficking and gating properties of AMPA receptors, and different isoforms display distinct expression patterns in brain. Here, we compared the effects of four Tduanyu37 isoforms on the kinetics of AMPA receptor currents. Each isoform slowed the deactivation of GluR1 currents, but the slowing was greatest with gamma-4 and gamma-8. Isoform-specific differences in desensitization were also observed that correlated with effects on deactivation. Tduanyu37 isoforms also differentially modulated responses to trains of glutamate applications designed to mimic high-frequency presynaptic firing. Importantly, whereas both stargazin and gamma-4 rescued excitatory synaptic transmission in cerebellar granule cells from stargazer mice, the decay of miniature EPSCs was 2-fold slower in neurons expressing gamma-4. The results show that heterogeneity in the composition of AMPA complexes contributes to synapse-specific differences in EPSC decays and frequency-dependent modulation of neurotransmission.

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