Kainate-induced elevations of intracellular Ca²⁺ and extracellular glutamate are partially decreased by NMDA receptor antagonists in cultured cerebellar granule neurons

Several lines of evidence indicate that physiological activity of N-methyl-D-aspartate (NMDA) receptor was blocked by physiological concentration of Mg²⁺ (1.2 mM). However, the activity of NMDA receptor may not be blocked totally with this concentration of Mg²⁺ under elevated membrane potential by kainate. Here, we described the effect of Mg²⁺ on NMDA receptor and how much of NMDA receptor functions could be activated by kainate. Effects of NMDA receptor antagonist on kainate-induced elevation of intracellular Ca²⁺ levels ([Ca²⁺]_i) and extracellular glutamate level were examined in cultured rat cerebellar granule neurons. Kainate-induced elevation of [Ca²⁺]_i was not affected by physiological concentration of Mg²⁺ though NMDA-induced elevation was blocked by the same concentration of Mg²⁺. Kainate-induced elevation of [Ca²⁺]_i was decreased by 32% in the presence of NMDA antagonists, MK-801 and CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid), in Mg²⁺ free buffer. Kainate receptor-activated glutamate release was also decreased (30%) by MK-801 or CPP. These results show that certain extent of elevations of intracellular Ca²⁺ and extracellular glutamate by kainate is due to coactivation of NMDA receptors.