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NMDA receptor subunit‐dependent modulation by conantokin‐G and Ala(7)‐conantokin‐G
Author(s) -
Ragnarsson L.,
Yasuda T.,
Lewis R. J.,
Dodd P. R.,
Adams D. J.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03574.x
Subject(s) - nmda receptor , glutamate receptor , receptor , protein subunit , biophysics , biology , xenopus , inhibitory postsynaptic potential , glutamic acid , biochemistry , microbiology and biotechnology , chemistry , amino acid , endocrinology , gene
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 μ m 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 EC 50 , 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.