NR1containing

NR1-containing refers to NMDA-type glutamate receptors that include the NR1 subunit, encoded by the GRIN1 gene. The NR1 subunit is obligatory for receptor assembly and channel function; without NR1, functional NMDA receptors do not form.

NMDA receptors are typically heterotetramers composed of two NR1 subunits and two additional subunits, most commonly NR2 or NR3. The NR1 subunit provides the binding site for glycine, a required co-agonist, while the NR2 subunits bind glutamate. The combination of NR1 with different NR2 or NR3 subunits endows each receptor with distinct kinetic and pharmacological properties, including magnesium block and calcium permeability. NR1 itself exists in multiple splice variants, such as NR1-1a and NR1-2b, which differ in regions that influence trafficking, regulation, and interaction with intracellular proteins.

Functionally, NR1-containing NMDA receptors mediate excitatory synaptic transmission and contribute to synaptic plasticity mechanisms such as long-term potentiation and long-term depression. Their activity is both ligand- and voltage-dependent, requiring co-agonist binding and relief of magnesium block for channel opening.

Pharmacologically, NR1-containing receptors are targets of various agents. Conventional antagonists and psychotropic drugs modulate their activity, while subunit composition can influence sensitivity to modulation.

Clinical relevance: Mutations or dysregulation of GRIN1, and thus NR1-containing receptors, are associated with neurodevelopmental disorders, epileptic encephalopathy, and intellectual disability. Research into NR1-containing receptors informs understanding of learning, memory, and potential therapeutic strategies for related conditions.