Sensitivity of cultured human embryonic cerebral cortical neurons to excitatory amino acid-induced calcium influx and neurotoxicity

1991 ◽  
Vol 542 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Mark P. Mattson ◽  
Barbara Rychlik ◽  
Jin Song You ◽  
Jesse E. Sisken
1991 ◽  
Vol 66 (1) ◽  
pp. 293-306 ◽  
Author(s):  
L. J. Larson-Prior ◽  
P. S. Ulinski ◽  
N. T. Slater

1. A preparation of turtle (Chrysemys picta and Pseudemys scripta) brain in which the integrity of the intracortical and geniculocortical pathways in visual cortex are maintained in vitro has been used to differentiate the excitatory amino acid (EAA) receptor subtypes involved in geniculocortical and intracortical synapses. 2. Stimulation of the geniculocortical fibers at subcortical loci produces monosynaptic excitatory postsynaptic potentials (EPSPs) in visual cortical neurons. These EPSPs are blocked by the broad-spectrum EAA receptor antagonist kynurenate (1-2 mM) and the non-N-methyl-D-aspartate (NMDA) antagonist 6, 7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), but not by the NMDA antagonist D,L-2-amino-5-phosphonovalerate (D,L-AP-5, 100 microM). These results indicate that the geniculocortical EPSP is mediated by EAAs that access principally, if not exclusively, EAA receptors of the non-NMDA subtypes. 3. Stimulation of intracortical fibers evokes compound EPSPs that could be resolved into three components differing in latency to peak. The component with the shortest latency was not affected by any of the EAA-receptor antagonists tested. The second component, of intermediate latency, was blocked by kyurenate and DNQX but not by D,L-AP-5. The component of longest latency was blocked by kynurenate and D,L-AP-5, but not by DNQX. These results indicate that the compound intracortical EPSP is comprised of three pharmacologically distinct components that are mediated by an unknown receptor, by quisqualate/kainate, and by NMDA receptors, respectively. 4. Repetitive stimulation of intracortical pathways at 0.33 Hz produces a dramatic potentiation of the late, D,L-AP-5-sensitive component of the intracortical EPSP. 5. These experiments lead to a hypothesis about the subtypes of EAA receptors that are accessed by the geniculocortical and intracortical pathways within visual cortex.


1978 ◽  
Vol 56 (3) ◽  
pp. 443-446 ◽  
Author(s):  
G. G. Yarbrough

Iontophoretically applied muscimol exerted a potent inhibitory action on the firing of spontaneously active cerebral cortical neurons of rats. On the basis of ejection currents employed, muscimol was considerably more potent than γ-aminobutyric acid (GABA), and the inhibitions produced by muscimol were frequently of a longer duration than those observed with GABA. Nipecotic acid and diaminobutyric acid (DABA) are potent inhibitors of high-affinity GABA uptake systems and muscimol is not thought to be a substrate for high-affinity GABA uptake (JOHNSTON, G. A. R. 1976. Physiolic pharmacology of GABA and its antagonists in the vertebrate nervous system. In GABA in nervous system function. Edited by E. Roberts, T. Chase, and D. B. Tower. Raven Press, New York). However, nipecotic acid and DABA consistently enhanced the inhibitory effects of both GABA and muscimol on cortical neurons while not affecting monoamine or adenosine 5′-monophosphate induced inhibitions. These findings suggest that iontophoretically applied nipecotic acid and DABA have some specificity for amino acid mechanisms in the cortex, but their actions appear to be more complex than can be explained by a selective blockade of GABA uptake processes. Thus, the uptake blockers may be exerting a weak and not readily detectable agonist action at amino acid receptors. Alternatively, the actions of iontophoretically applied muscimol may be partially terminated by uptake through GABA uptake systems.


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