Role of Calcium ions in Nickel potentiation of NMDA currents

NMDA receptors are glutamate-gated channels distributed throughout the brain in the excitatory synapses and are critical for the nervous system function. They are assembled from two types of subunits, the essential NR1 and at least one NR2(A,B,C,D). Nickel (Ni) modulates the current flowing through NMDA receptors in a different way depending on the NR2 subunit present. We have recently identified several domains of the channel involved in Ni interaction, but many aspects of this modulation remain elusive. In this work we intended to determine the role of calcium (Ca) ions in the potentiation induced by Ni on the current through NR1/NR2B recombinant NMDA receptors. When Ni was applied in the presence of the physiological concentration of Ca (1.8 mM), a voltage-independent potentiation of the current was observed with a Kp of 2.5 µM. This effect was progressively reduced by decreasing Ca concentrations and it was no more detectable with 0.18 mM Ca or in the presence of barium (Ba, 0.3 mM). In this last case the effect of Ni on NR1/NR2B receptors was mainly inhibitory (Ki(- 60mV)=156µM). Therefore a physiological concentration of Ca is necessary to induce Ni amplification of the current. Many data in the literature indicate a correlation between Ca ion entrance through the channel, NMDA current facilitation and cytoskeleton; however, in our experiments, the application of the actin perturbing agent cytochalasin-D did not produce major modifications in Ni effect.