Journal of Neuroscience, Vol 9, 70-80, Copyright © 1989 by Society for Neuroscience
Separation of quisqualate- and kainate-selective glutamate receptors in cultured neurons from the rat superior colliculus
M Perouansky and R Grantyn
Department of Neurophysiology, Max Planck Institute for Psychiatry, Martinsried, Federal Republic of Germany.
The aim of the present study was to identify and characterize the receptors
and ionic channels mediating the compound response of tectal neurons to
exogenous L-glutamate (Glu). Particular attention was paid to the question
of whether separate receptors and channels exist for quisqualate (QA) and
kainate (KA) and, if so, whether binding to one of these receptors would
modify the response elicited through the other. Neurons were dissociated
from the superficial gray layer of the superior colliculus from E21 or P1
rats. Between days 14 and 21 in vitro, responsiveness of tectal neurons to
Glu and related substances was tested by recording the whole-cell currents
induced by rapid superfusion with drug-containing salt solutions. Our
experiments showed that tectal neurons express at least 3 distinct types of
receptors for acidic amino acids. KA-activated currents (I(KA)) differ from
QA- activated currents (I(QA)) in their dose-response characteristics,
desensitization patterns, selective blockade with kynurenic acid and
suppression by elevated [Ca2+]o, I(KA), but not I(QA), is significantly
reduced by low levels of [Cl-]o, and the [Cl-]o-dependent shift of the
reversal potential for I(KA) suggests that KA promotes a conductance
decrease for Cl-. Such an effect has been ascribed to APB-receptors, but
L-2-amino-4-phosphonobutyrate (APB) itself failed to induce current
responses in tectal neurons. KA was without effect when administered
together, and in equimolar concentrations, with QA. The block of I(KA) was,
however, surmounted by applying KA at considerably higher concentrations.
It is concluded that QA acts as a low-affinity competitive antagonist at
the KA site and as a high-affinity agonist at its own receptor. The
response to the endogenous ligand Glu reflects properties of all receptors.
QA and KA receptors account for 20-30% (QA) and 49-82% (KA) of the compound
current elicited with 100 microM Glu. These results indicate that binding
of Glu does not, in contrast to QA, produce any significant suppression of
the KA-receptor-mediated current component.
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