Calcium-permeable AMPA and kainate receptors of GABAergic neurons

This Commentary presents a brief discussion of the action of glutamate calcium permeable receptors present with neurons on the release of the neurotransmitter gamma-aminobutyric acid (GABA). In particular, Glutamate sensitive Kainic Acid Receptors (KARs) and α-Amino-3-hydroxy-5-Methyl-4-isoxazole Propionic Acid Receptor (AMPARs) are Na⁺ channels that typically cause neuronal cells to depolarize and release GABA. Some of these receptors are also permeable to Ca²⁺ and are hence involved in the calcium-dependent release of GABA neurotransmitters. Calcium-permeable kainate and AMPA receptors (CP-KARs and CP-AMPARs) are predominantly located in GABAergic neurons in the mature brain and their primary role is to regulate GABA release. AMPARs which do not contain the GluA2 subunit are mainly localized in the postsynaptic membrane. CP-KAR receptors are located mainly in the presynapse. GABAergic neurons expressing CP-KARs and CP-AMPARs respond to excitation earlier and faster, suppressing hyperexcitation of other neurons by the advanced GABA release due to an early rapid [Ca²⁺]_i increase. CP-AMPARs have demonstrated a more pronounced impact on plasticity compared to NMDARs because of their capacity to elevate intracellular Ca²⁺ levels independently of voltage. GABAergic neurons that express CP-AMPARs contribute to the disinhibition of glutamatergic neurons by suppressing GABAergic neurons that express CP-KARs. Hence, the presence of glutamate CP-KARs and CP-AMPARs is crucial in governing hyperexcitation and synaptic plasticity in GABAergic neurons.