Kainate receptor

A kainate receptor is an ionotropic receptor activated by the neurotransmitter glutamate. Activation opens an ion channel, coupling chemical recognition to an electrical response. The family is named after kainic acid, an experimental agonist. Kainate receptors and AMPA receptors are distinct receptor families even though some experimental agonists can activate both, making pharmacological responses alone difficult to interpret.^[ref]

A genetic experiment helped isolate the kainate component. C. Mulle and colleagues generated mice lacking the subunit then called GluR6. Neurons in the hippocampal CA3 region became much less sensitive to kainic acid; a postsynaptic kainate current evoked by a train of mossy-fibre stimulation was absent in the mutants. This linked a molecular subunit to a synaptically evoked response, rather than merely to a response produced by bathing tissue in an agonist.^[ref] The subunit's current name is GluK2.^[ref]

For example, a current produced by an agonist that also activates AMPA receptors cannot be assigned wholly to kainate receptors. Comparing selective perturbations with synaptic stimulation supplies stronger evidence for the receptor responsible. In another experimental setting, paired recordings in ground-squirrel retina showed that AMPA receptors and kainate receptors could route cone signals into OFF retinal bipolar cells with different temporal filtering properties.^[ref]

GluK2 is a subunit of the kainate receptor family of glutamate-gated ion channels. The human subunit is encoded by GRIK2; the older name GluR6 occurs in much of the originating experimental literature. A receptor subunit is a component of an assembled channel, not a synonym for every member of the kainate receptor family.^[ref]

Deleting the gene for the subunit gave a direct test of its functional contribution. C. Mulle and colleagues generated GluR6-deficient mice and found reduced sensitivity to kainic acid in hippocampal CA3 neurons. A postsynaptic kainate current evoked by trains of mossy-fibre stimulation was absent in the mutants. The mice were also less susceptible to the tested systemic-kainate seizure challenge.^[ref]

For an experimental comparison, disappearance of a stimulus-evoked current after deleting GluK2 supports a requirement for that subunit in the tested response. It does not establish that every excitatory current in the same cell is a GluK2 current: AMPA receptors and other receptors can still contribute different components. Nor does gene deletion, by itself, specify the subunit composition of every remaining channel. Combining molecular perturbation with a precisely defined stimulation protocol makes the inference much stronger than interpreting an agonist response alone.