Comparing the impact of an acute exercise bout on plasma amino acid composition, intraerythrocytic Ca2+ handling, and red cell function in athletes and untrained subjects

- Cycling to exhaustion bout produces release of glutamate into the circulation.
- Activation of NMDA receptors in red cells by glutamate triggers Ca2+ uptake.
- Ca2+ uptake mediates a transient decrease in hemoglobin oxygen affinity.
- High plasma post-exercise glutamate is associated with increase red cell instability and hemolysis

The N-methyl d-aspartate receptors (NMDARs) mediating Ca2+ uptake upon stimulation with glutamate and glycine were recently discovered in red blood cells (RBC) of healthy humans. Activation of these receptors with agonists triggered transient Ca2+-dependent decrease in hemoglobin oxygen affinity in RBC suspension. The aim of this study was to assess the potential physiological relevance of this phenomenon. Two groups formed by either healthy untrained volunteers or endurance athletes were subjected to a stepwise incremental cycling test to exhaustion. Plasma glutamate levels, activity of the NMDARs, and hemoglobin O2 affinity were measured in blood samples obtained before and after the exercise in both groups. Increase in plasma glutamate levels following exercise was observed in both groups. Transient Ca2+ accumulation in response to the NMDAR stimulation with NMDA and glycine was followed by facilitated Ca2+ extrusion from the RBC and compensatory decrease in cytosolic Ca2+ levels. Short-term activation of the receptors triggered a transient decrease in O2 affinity of hemoglobin in both groups. These exercise-induced responses were more pronounced in athletes compared to the untrained subjects. Athletes were initially presented with lower basal intracellular Ca2+ levels and hemoglobin oxygen affinity compared to non-trained controls. High basal plasma glutamate levels were associated with induction of hemolysis and formation of echinocytes upon stimulation with the receptor agonists. These findings suggest that glutamate release occurring during exhaustive exercise bouts may acutely facilitate O2 liberation from hemoglobin and improve oxygen delivery to the exercising muscle.

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