Functional NMDA receptors in rat erythrocytes

Abstract

N-methyl-d-aspartate (NMDA) receptors are ligand-gated nonselective cation channels mediating fast neuronal transmission and long-term potentiation in the central nervous system. These channels have a 10-fold higher permeability for Ca(2+) compared with Na(+) or K(+) and binding of the agonists (glutamate, homocysteine, homocysteic acid, NMDA) triggers Ca(2+) uptake. The present study demonstrates the presence of NMDA receptors in rat erythrocytes. The receptors are most abundant in both erythroid precursor cells and immature red blood cells, reticulocytes. Treatment of erythrocytes with NMDA receptor agonists leads to a rapid increase in intracellular Ca(2+) resulting in a transient shrinkage via Gardos channel activation. Additionally, the exposure of erythrocytes to NMDA receptor agonists causes activation of the nitric oxide (NO) synthase facilitating either NO production in l-arginine-containing medium or superoxide anion (O(2)(.-)) generation in the absence of l-arginine. Conversely, treatment with an NMDA receptor antagonist MK-80, or the removal of Ca(2+) from the incubation medium causes suppression of Ca(2+) accumulation and prevents attendant changes in cell volume and NO/O(2)(.-) production. These results suggest that the NMDA receptor activity in circulating erythrocytes is regulated by the plasma concentrations of homocysteine and homocysteic acid. Moreover, receptor hyperactivation may contribute to an increased incidence of thrombosis during hyperhomocysteinemia.

Stimulation of human red blood cells leads to Ca2+-mediated intercellular adhesion

“…An example is the vasco-occlusive crisis of sickle cell disease (SCD) patients. Here, the Ca 2+ influx is mediated by the NMDA-receptor, which has been found to be abundant in RBCs [46]. Our study provides a link between the increased prevalence of the NMDA-receptor in SCD patients [50] and the symptoms of the vascoocclusive crisis.…”

“…The dependence on high Ca 2+ concentrations and evidence from further studies reporting enhanced aggregation of PS liposomes in the presence of polymers [42] suggest that additional membrane constituents in the RBC contribute to the aggregation process. This leads to other Ca 2+ -dependent proteins in RBCs, such as PKC α [43,44] or the nitric oxide synthase [45,46]. Further research is required to address the question of the molecular identity of the additional components in the adhesion process.…”

Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes

“…The voltageindependent cation channels were shown to be partially related to TRPC3/6/7 channels (Foller et al 2008). Recent data demonstrated the existence of NMDA receptors in rat (Makhro et al 2010) and AMPA receptors in human (Föller et al 2009) erythrocytes. In our recent study (Kucherenko and Lang 2010) we have shown that an AMPA receptor antagonist NASRM (1-naphthyl acetyl spermine) was effective not only in blocking cation currents induced by Cl -removal but also significantly blunted the basal cation conductance in Cl --containing bath solution.…”

Effect of Propofol and Memantine on Erythrocyte Deformability in Diabetic Rat Model

“…The presence of functional NMDA Rec on erythroid precursors and mature erythrocytes is shown by Makhro and colleagues (11). In their study, they demonstrated a calcium influx in a subgroup of cells in response to NMDA, which in turn triggered changes in cell volume and nitric oxide (NO) synthesis.…”

“…Activation of NMDA Rec resulted in volume changes, changes in cytoskeleton and nitric oxide synthesis (11).…”