Ca2 ⁺ Permeability of KA-AMPA—Gated Glutamate Receptor Channels Depends on Subunit Composition

TLDR

Non‑NMDA glutamate receptors, traditionally thought to conduct only monovalent cations, include KA/AMPA‑gated channels composed of GluR1, GluR2, and GluR3 subunits, whereas NMDA receptors form a distinct class. The authors expressed various combinations of GluR1, GluR2, and GluR3 subunits in Xenopus oocytes to assess their permeability to divalent cations. KA and AMPA induced inward Ca²⁺ currents only in oocytes expressing GluR1, GluR3, or GluR1+GluR3, but not in those containing GluR2, indicating that specific subunit compositions enable calcium‑dependent signaling through non‑NMDA receptors.

Abstract

NMDA ( N -methyl -D-aspartate) receptors and non-NMDA receptors represent the two major classes of ion channel-linked glutamate receptors. Unlike the NMDA receptor channels, non-NMDA receptor channels have usually been thought to conduct monovalent cations only. Non-NMDA receptor ion channels that can be gated by kainic acid (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) are formed by the glutamate receptor subunits GluR1, GluR2, and GluR3. These subunits were expressed in various combinations in Xenopus oocytes so that their permeability to divalent cations could be studied. At physiological resting potentials, KA and AMPA elicited inward calcium currents in oocytes expressing GluR1, GluR3, and GluR1 plus GluR3. In contrast, oocytes expressing GluR1 plus GluR2 or GluR3 plus GluR2 showed no such permeability. Thus, in neurons expressing certain KA-AMPA receptor subunits, glutamate may trigger calcium-dependent intracellular events by activating non-NMDA receptors.