role of serine phosphorylation on the slow inactivation of the GluR1 Lurcher AMPA receptor.

AMPA receptors are the main fast excitatory neurotransmitter receptors in the CNS. The Lurcher mutation is a single amino acid switch that occurs in glutamate receptor subunits. When introduced to the GluR1 glutamate receptor subunit, the Lurcher mutation (GluR1Lc) results in constitutively active channels that undergo a slow process of inactivation that is not seen in wild type channels. GluR1 subunits are phosphorylated by PKC (at Ser831) and PKA (at Ser845). In the present study 1 evaluated the rote of GluR1Lc phosphorylation on the rate of receptor inactivation. Activation of PKC resulted in decreased rates of inactivation, while blocking PKC resulted in increased inactivation rates. Blocking the phosphatase calcineurin resulted in increased inactivation rates. Western blot analysis showed that phosphorylation of Ser831 increases with induction of inactivation while Ser845 phosphorylation decreases. This study implies that the state of phosphorylation of GluR1Lc receptors dictates the rate of receptor inactivation.