High sensitivity of cerebellar neurons to homocysteine is determined by expression of GluN2C and GluN2D subunits of NMDA receptors.

High sensitivity of cerebellar neurons to homocysteine is determined by expression of GluN2C and GluN2D subunits of NMDA receptors. Biochem Biophys Res Commun. 2018 Nov 30;506(3):648-652 Authors: Sibarov DA, Giniatullin R, Antonov SM Abstract Homocysteine (HCY) induced neurotoxicity largely depends on interaction of this endogenous amino acid with glutamate NMDA receptors (NMDARs). This receptor type is composed by GluN1 and different GluN2 (A, B, C or D) subunits. However, the receptor activity of HCY in brain regions which differ in relative contribution of GluN2 subunits was not tested so far. In the current study, we explored the action of HCY on cerebellar neurons which natively express GluN2C and GluN2D subunits of NMDARs and compared this with the action of HCY on cortical neurons which are mainly composed by GluN2A and GluN2B subunits. To validate obtained results, we also studied the responses to HCY in recombinant GluN1/2C and GluN1/2D NMDARs expressed in HEK293T cells. Responses to HCY were compared to membrane currents evoked by glutamate or by the specific agonist NMDA. First, we found that on HEK cells expressing GluN1/2C or GluN1/2D NMDARs, HCY was full agonist producing membrane currents similar in amplitude to currents induced by glutamate. The EC50 values for these particular receptor subtype activation were 80 μM and 31 μM, respectively. Then, we found that HCY similarly to NMDA, evoked large slightly desensi...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research