Excessive consumption of Lathyrus sativus L. seeds can cause neurolathyrism, a disease endemic to Ethiopia. This neurodegenerative disorder is characterized by spastic paraparesis of the legs due to motor neuron degeneration. Chronic exposure to the neurotoxin beta-N-oxalyl-alpha,beta-diaminopropionic acid (beta-ODAP) present in the seeds is proposed as the cause of the disease but the mechanism of its action has not been conclusively explained. Beta-ODAP is a glutamate analogue at AMPA/KA receptors in neurons and therefore potentially acts as an excitotoxic substance. A key factor in excitotoxic neuronal cell death is a disturbance of the intracellular Ca²⁺ homeostasis. Excessive Ca²⁺ uptake leads to sequestration into mitochondria, generation of reactive oxygen species (ROS), opening of the permeability transition pore and release of the apoptotic mediator cytochrome C. We found that chronic exposure of N2a neuroblastoma cells to beta-ODAP enhanced mitochondrial Ca²⁺ uptake following stimulation of the cells with bradykinin. The photoprotein aequorin, specifically targeted to mitochondria, was used to measure mitochondrial Ca²⁺ influx – similarly we found that cytoplasmic Ca²⁺ changes triggered by bradykinin were larger in beta-ODAP treated cells and Ca²⁺ uptake in the ER was also increased. The enhanced ER Ca²⁺ uptake may possibly result from upregulation of the sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) by beta-ODAP, as confirmed by Western Blot analysis. The working hypothesis is that beta-ODAP increases the ER Ca²⁺ content, causing enhanced ER Ca²⁺ release and increased Ca²⁺ uptake in mitochondria, which may ultimately lead to apoptosis. Further work is directed towards the mechanisms of beta-ODAP-triggered stimulation of SERCA and how this may lead to neurodegeneration.