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TA Verdoorn and R Dingledine
Department of Pharmacology and Neurobiology Curriculum, University of North Carolina, Chapel Hill 27599.
The properties of excitatory amino acid (EAA) receptors transplanted into Xenopus oocytes were investigated by voltage clamp 48 hr to 5 days after oocytes had been injected with mRNA isolated from rat brain. The application of EAA agonists to mRNA-injected cells, but not to uninjected or water-injected cells, produced several different inward currents, two of which are characteristic of neuronal EAA receptors. Currents with properties expected from activation of N-methyl-D- aspartate (NMDA) receptors were evoked by L-glutamate (EC50 = 2.3 microM), D-aspartate (10 microM), L-aspartate (13 microM), NMDA (31 microM), and ibotenate (35 microM). Inward currents activated by these agonists were blocked by Mg2+ in a voltage-dependent manner and antagonized by 10-50 microM D-2-amino-5-phosphonovaleric acid (D-APV). The D-APV block was not voltage dependent. A second type of inward current was produced by kainate, domoate, (RS)-alpha-amino-3-hydroxy-5- methyl-4-isoxazolepropionate (AMPA), and L-glutamate. This smooth inward current was insensitive to Mg2+ and D-APV. L-Glutamate and domoate were equipotent for activating this current (EC50 = 14 microM) whereas kainate was less potent (98 microM). The kainate potency was somewhat voltage dependent, inasmuch as the EC50 was 33% lower when measured at +38 mV than when measured at -60 mV in the same cells. Quisqualate (50 microM) and AMPA (50 microM) drastically reduced the kainate current, suggesting these agonists also interact with this receptor. Some mRNA preparations encoded only receptors for the kainate response, which argues for distinct NMDA and non-NMDA receptors. A third type of inward current was produced by quisqualate. This current, consisting of oscillating and smooth components, was carried by chloride and not evoked by AMPA, suggesting it is not likely caused by activation of the conventional neuronal quisqualate receptor. The utility of the oocyte preparation for quantitative pharmacological studies of EAA receptors is discussed.
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