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A quantitative study of the actions of excitatory amino acids and antagonists in rat hippocampal slices
Author(s) -
Blake J.F.,
Brown M.W.,
Collingridge G.L.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb16576.x
Subject(s) - kainate receptor , ampa receptor , excitatory postsynaptic potential , cnqx , kynurenic acid , nmda receptor , biophysics , chemistry , glutamate receptor , excitatory amino acid antagonists , inhibitory postsynaptic potential , neuroscience , pharmacology , biology , biochemistry , receptor
1 A quantitative pharmacological investigation of the actions of excitatory amino acids on hippocampal CA1 neurones has been made using a new slice preparation developed for grease gap recording; d.c. potential was measured across a grease barrier placed between alvear fibres and the bathing medium. 2 In Mg 2+ ‐free perfusate, N‐methyl‐D‐aspartate (NMDA, 1–100 μ M ), quisqualate (1–500 μ M ), kainate (1–200 μ M ) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA, 1–100 μ M ) caused dose‐dependent depolarizations. 3 The dose‐response relationships were fitted to logistic expressions. The maximum responses to AMPA, NMDA and kainate were similar; their respective EC 50 values were 5, 13 and 23 μ M . Quisqualate had a smaller maximum; its EC 50 value was 10 μ M . The slopes of the dose‐response relationships were different for the 4 agonists; the order of steepness of the slopes was NMDA > AMPA > kainate > quisqualate. 4 Similar amino acid‐induced depolarizations were observed in slices of just the CA1 region or in whole slices bathed in tetrodotoxin. Isolated alvear fibres, however, were insensitive to the excitatory amino acids. 5 D‐2‐Amino‐5‐phosphonovalerate (APV, 50 μ M ) selectively and reversibly antagonized responses induced by NMDA (apparent pA 2 = 5.21). 6 Kynurenic acid (1 mM) reversibly depressed responses to the three agonists tested. The doseratios for antagonism of AMPA, kainate and quisqualate were 6.9, 5.6 and 4.6 respectively. 7 This preparation has a different sensitivity profile to agonists from those of previously reported preparations of spinal cord, neocortex and cerebellum. The greater sensitivity to NMDA may be due to the higher density of NMDA receptors in the hippocampus. The effects of the antagonists, APV and kynurenate, are similar to those found in other brain areas.