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ZD7288 inhibits postsynaptic glutamate receptor‐mediated responses at hippocampal perforant path–granule cell synapses
Author(s) -
Chen Chu
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.0953-816x.2003.03174.x
Subject(s) - perforant path , neuroscience , long term potentiation , excitatory postsynaptic potential , neurotransmission , hippocampal formation , glutamate receptor , postsynaptic potential , granule cell , biology , chemistry , inhibitory postsynaptic potential , receptor , dentate gyrus , biochemistry
Hyperpolarization‐activated channels (I h ) are widely expressed in the nervous system and believed to play an important role in the regulation of membrane excitability and rhythmic activity. Recent evidence suggests that I h may be involved in long‐term potentiation (LTP) in the hippocampus; however, the results are controversial. To explore the possible causes of these differing results, the effects of I h blockers on synaptic activity were evaluated in mouse hippocampal slices. ZD7288 (20 µ m ), a selective I h blocker, apparently prevented the induction of LTP, while Cs + (1 m m ), a commonly used I h blocker, had no effect on LTP at hippocampal perforant path–dentate granule cell synapses. In addition, ZD7288 but not Cs + abolished basal synaptic transmission. Results from voltage‐clamp experiments showed that ZD7288 produced a very little inhibition on hyperpolarization‐activated currents, indicating a weak expression of the I h in granule neurons. Outside‐out patch recordings revealed that ZD7288 inhibited glutamate receptor‐mediated responses, while Cs + had no effect on them. Meanwhile, ZD7288 reduced both α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and N ‐methyl‐ d ‐aspartate receptor‐mediated excitatory postsynaptic currents. The results suggest that ZD7288‐induced reduction of synaptic transmission may result from its inhibition of the postsynaptic glutamate receptors on dentate granule neurons.