title: Adenosinergic depression of glutamatergic transmission in the entorhinal cortex of juvenile rats via reduction of glutamate release probability and the number of releasable vesicles.
abstract: Adenosine is an inhibitory neuromodulator that exerts antiepileptic effects in the brain and the entorhinal cortex (EC) is an essential structure involved in temporal lobe epilepsy. Whereas microinjection of adenosine into the EC has been shown to exert powerful antiepileptic effects, the underlying cellular and molecular mechanisms in the EC have not been determined yet. We tested the hypothesis that adenosine-mediated modulation of synaptic transmission contributes to its antiepileptic effects in the EC. Our results demonstrate that adenosine reversibly inhibited glutamatergic transmission via activation of adenosine A1 receptors without effects on GABAergic transmission in layer III pyramidal neurons in the EC. Adenosine-induced depression of glutamatergic transmission was mediated by inhibiting presynaptic glutamate release probability and decreasing the number of readily releasable vesicles. Bath application of adenosine also reduced the frequency of the miniature EPSCs recorded in the presence of TTX suggesting that adenosine may interact with the exocytosis processes downstream of Ca(2+) influx. Both Gαi/o proteins and the protein kinase A pathway were required for adenosine-induced depression of glutamatergic transmission. We further showed that bath application of picrotoxin to the EC slices induced stable epileptiform activity and bath application of adenosine dose-dependently inhibited the epileptiform activity in this seizure model. Adenosine-mediated depression of epileptiform activity was mediated by activation of adenosine A1 receptors and required the functions of Gαi/o proteins and protein kinase A pathway. Our results suggest that the depression of glutamatergic transmission induced by adenosine contributes to its antiepileptic effects in the EC.
authors.affiliation: Department of Pharmacology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, North Dakota, United States of America.
authors.forename: Shouping
authors.initials: S
authors.lastname: Wang
authors.forename: Lalitha
authors.initials: L
authors.lastname: Kurada
authors.forename: Nicholas I
authors.initials: NI
authors.lastname: Cilz
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Chen
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Xiao
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
authors.forename: Saobo
authors.initials: S
authors.lastname: Lei
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D018728:Entorhinal Cortex / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D000241:Adenosine