Introduction to GRIK disorder

The KARs and AMPARs are the most closely related members within the iGluR family. Similar to AMPARs, KARs pass very short and fast electrical currents. However they differ in their location on brain cells, how they respond to rapid groups of signals and the specific processes they regulate. They are involved in the overall control of various aspects of brain excitability and memory formation.

The majority of known GRIK disorder cases involve GRIK2, in particular, GoF GRIK2 variants. These patients have KAR signals that are excessively prolonged and therefore cause too much excitation. Unlike healthy brains where glutamate binds to KARs for a short time, in GRIK disorder patients, glutamate binds for an extended period, causing damaging changes in the signals produced.

As with NMDARs and AMPARs, KARs are commonly composed of different subunits (e.g. KARs made from two GluK2 subunits and two GluK5 subunits). Like AMPARs, KARs can also be made exclusively from the same subunit (e.g. only GluK1 or only GluK2). Even though GRIK disorder kids have one healthy copy of the affected gene, most of their receptors will nonetheless contain at least one variant subunit. A receptor likely only needs one of its four subunits to be a variant for its properties to be affected.

There are currently no specific treatments for GRIK disorder patients. Instead symptoms are managed with other types of medications. While Perampanel, an AMPAR inhibitor, can also inhibit some forms of KARs, it’s effectiveness in GRIK disorder is yet to be demonstrated.