Ca2+ permeable AMPA receptors switch allegiances: mechanisms and consequences

The subunit composition of synaptic AMPA receptors can undergo dynamic changes during physiological functioning and under pathological conditions. This switch in AMPA receptor phenotype involves changes in the level of GluA2 subunits that are mediated via regulated AMPA receptor trafficking, modification of local protein synthesis and altered gene transcription of GluA2 subunits. Incorporation of the GluA2 subunits into an AMPA receptor alters a number of key biophysical properties, including Ca2+ permeability and the waveform of the synaptic current. These changes alter the ability of synaptic currents to evoke an action potential and therefore have a profound effect on the computational capability of individual neurons and thus the output of neuronal circuits.