(R)-CPP, NMDA antagonist

• FuncS

PubMed

Functional Studies - (R)-CPP, NMDA antagonist (AB120159)

Transporter blockade does not reveal an ambient glutamate concentration gradient between extracellular compartments.

A. Average Ca²⁺ increase in a spine during a 40 ms voltage step, with iontophoresis of L-aspartate (black), without iontophoresis (red), a second L-aspartate application (gray), L-aspartate in the presence of 100 μM TBOA (blue), and TBOA alone (green).

B. Comparison of spine Ca²⁺ transients in each condition, normalized to the first response to L-aspartate iontophoresis (n = 5). Error bars indicate SEM. Significance determined by Friedman ANOVA with Conover posthoc test : *p<0.05; **p<0.01; ***p<0.001.

If the extrasynaptic glutamate concentration is higher than that in the cleft because transporters prevent diffusion of glutamate into the synapse, blocking transporters should result in a large Ca²⁺ increase in the spine as extrasynaptic glutamate rushes into the cleft and activates synaptic NMDARs. Spines exhibited a Ca²⁺ increase during a 40 ms depolarization with iontophoresis of the glutamate transporter substrate and NMDAR agonist, L-aspartate (A; black and gray traces), confirming the presence of NMDARs. However, TBOA (100 μM) did not increase the Ca²⁺ transient in the same spines during the 40 ms depolarization when compared to the control voltage step without L-aspartate iontophoresis (See image compare green and red traces; 20.6±13.62%; p>0.5; n = 5;). TBOA was effective in blocking transporters, however, as the NMDAR-mediated Ca²⁺ signal evoked by iontophoresis of L-aspartate was increased in the presence of TBOA (See image). This result indicates that glutamate transporters do not normally generate a concentration gradient of ambient glutamate between extrasynaptic and synaptic extracellular compartments.

Herman et al PLoS One. 2011;6(11):e26501. doi: 10.1371/journal.pone.0026501. Epub 2011 Nov 1. Fig 3. Reproduced under the Creative Commons license http://creativecommons.org/licenses/by/4.0/

• Chemical Structure

Lab

Chemical Structure - (R)-CPP, NMDA antagonist (AB120159)

2D chemical structure image of ab120159, (R)-CPP, NMDA antagonist