NMDA receptor subunit-dependent modulation by conantokin-G and Ala(7)-conantokin-G

Authors

L Ragnarsson, University of Queensland
Takahiro Yasuda, RMIT University
Richard J. Lewis, University of QueenslandFollow
P R. Dodd, University of Queensland
David J. Adams, University of QueenslandFollow

RIS ID

105734

Publication Details

Ragnarsson, L., Yasuda, T., Lewis, R. J., Dodd, P. R. & Adams, D. J. (2006). NMDA receptor subunit-dependent modulation by conantokin-G and Ala(7)-conantokin-G. Journal of Neurochemistry, 96 (1), 283-291.

Abstract

The modulation of recombinant NMDA receptors by conantokin-G (con-G) and Ala(7)-conantokin-G (Ala(7)-Con-G) was investigated in Xenopus oocytes injected with capped RNA coding for NR1 splice variants and NR2 subunits using the two-electrode voltage clamp technique. Glutamate exhibited a marginally higher apparent affinity for NR2A-containing receptors than NR2B-containing receptors, regardless of the NR1 subunit present. Conantokins were bath applied to give cumulative concentration responses in the presence of 3 and 30 μM glutamate. Both contantokins exhibited biphasic concentration-response relationships at NR2A-containing NMDA receptors, producing potentiation at low conantokin concentrations and inhibition at high concentrations. These effects were stronger with glutamate concentrations near its EC50, and less marked at saturating concentrations. In contrast, the conantokin concentration- response relation was monophasic and inhibitory at NR2B-containing receptors. We conclude that the combinations of subunits that comprise the NMDA receptor complex influence conantokin and glutamate affinities and the nature of the responses to conantokins.