ZD7288 inhibits postsynaptic glutamate receptor-mediated responses at hippocampal perforant path-granule cell synapses.
Hyperpolarization-activated channels (Ih) 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 Ih 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 Ih blockers on synaptic activity were evaluated in mouse hippocampal slices. ZD7288 (20 micro m), a selective Ih blocker, apparently prevented the induction of LTP, while Cs+ (1 mm), a commonly used Ih 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 Ih 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 alpha-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.
Neuroscience Center, School of Medicine, Louisiana State University Health Sciences Center, 2020 Gravier Street, Suite D, New Orleans, LA 70112, USA. cchen@lsuhsc.edu
Chu
C
Chen
D000704:Analysis of Variance; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D004553:Electric Conductivity; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000187:drug effects* / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D002316:Cardiotonic Agents; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011743:Pyrimidines; D011810:Quinoxalines; D017470:Receptors, Glutamate; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C082246:ICI D2788; D002586:Cesium; D018698:Glutamic Acid