title: Baclofen and adenosine inhibition of synaptic transmission at CA3-CA1 synapses display differential sensitivity to K+ channel blockade.
abstract: The metabotropic GABA(B) and adenosine A(1) receptors mediate presynaptic inhibition through regulation of voltage-dependent Ca(2+) channels, whereas K(+) channel regulation is believed to have no role at the CA3-CA1 synapse. We show here that the inhibitory effect of baclofen (20 μM) and adenosine (300 μM) on field EPSPs are differentially sensitive to Cs(+) (3.5 mM) and Ba(2+) (200 μM), but not 4-aminopyridine (100 μM). Barium had no effect on paired-pulse facilitation (PPF) in itself, but gave significant reduction (14 ± 5%) when applied in the presence of baclofen, but not adenosine, suggesting that the effect is presynaptic and selective on the GABA(B) receptor-mediated response. The effect of Ba(2+) on PPF was not mimicked by tertiapin (30 nM), indicating that the underlying mechanism does not involve GIRK channels. Barium did not affect PPF in slices from young rats (P7-P8), suggesting developmental regulation. The above effects of Ba(2+) on adult tissue were reproduced when measuring evoked whole-cell EPSCs from CA1 pyramidal neurons: PPF was reduced by 22 ± 3% in the presence of baclofen and unaltered in adenosine. In contrast, Ba(2+) caused no significant change in frequency or amplitude of miniature EPSCs. The Ba(2+)-induced reduction of PPF was antagonized by LY341495, suggesting metabotropic glutamate receptor involvement. We propose that these novel effects of Ba(2+) and Cs(+) are exerted through blockade of inwardly rectifying K(+) channels in glial cells, which are functionally interacting with the GABA(B) receptor-dependent glutamate release that generates heterosynaptic depression.
authors.affiliation: Department of Physiology and Biophysics, Aarhus University, 8000, Århus C, Denmark.
authors.forename: Jane
authors.initials: J
authors.lastname: Skov
authors.forename: Mogens
authors.initials: M
authors.lastname: Andreasen
authors.forename: John J
authors.initials: JJ
authors.lastname: Hablitz
authors.forename: Steen
authors.initials: S
authors.lastname: Nedergaard
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D001514:Bee Venoms / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000596:Amino Acids; D001514:Bee Venoms; C114624:LY 341495; D026902:Potassium Channel Blockers; D043682:Receptor, Adenosine A1; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; D002586:Cesium; D001464:Barium; C053907:8-cyclopentyl-1,3-dimethylxanthine; C029738:tertiapin; D015761:4-Aminopyridine; D013806:Theophylline; D001418:Baclofen; D000241:Adenosine