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Department of Physiology and Molecular Biophysics, Columbia University, New York, NY 10032.

1. The effects of lanthanum ions (La3+) on voltage-gated calcium currents (VGCCs) and excitatory amino acid (EAA)-evoked currents were characterized using cultured or acutely dissociated neurons from the dorsal horn of the rat spinal cord. 2. VGCCs evoked by depolarizing voltage steps were reversibly blocked by La3+ with an apparent log dissociation constant Kd of 163 nM. 3. La3+ antagonism of currents evoked by NMDA was less potent, with an EC50 (half-maximal effective concentration) of 2 microM. The block of NMDA-evoked currents was voltage independent and non-competitive with respect to activation of the NMDA receptor. 4. La3+ had both enhancing and blocking actions on currents evoked by kainate or by quisqualate; concentrations of La3+ between 1 and 100 microM enhanced kainate- and quisqualate-evoked currents, while the currents were blocked by concentrations of La3+ greater than 100 microM. Both the blocking and the enhancing actions of La3+ were independent of membrane potential. 5. An enhancing dose of La3+ shifted the dose-response curve for kainate to lower concentrations of agonist without changing the maximum evoked current, and a similar leftward shift of the quisqualate dose-response curve occurred at non-saturating concentrations of quisqualate. This enhancement might occur either due to increased affinity of the receptor for ligand, or by increased concentration of ligand at the membrane surface; the latter effect could result from a reduction in the membrane surface charge. 6. The divalent cation Zn(2+)-mimicked the effects of La3+ on excitatory amino acid-evoked currents in dorsal horn neurons, but was less potent both as a blocker and as an enhancer. This suggests that La3+ and Zn2+ could act with different potencies at the same site or sites, and that La3+ may be a useful probe for the mechanisms of Zn2+ effects. 7. Since La3+ enhances kainate- and quisqualate-evoked responses at the same concentrations at which it suppresses VGCCs (and NMDA-gated currents), it can be a useful probe for separating VGCC activation from kainate- and quisqualate-induced depolarizations in experiments where voltage clamp is impractical.

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