title: Involvement of inward rectifier and M-type currents in carbachol-induced epileptiform synchronization.
abstract: Exposure to cholinergic agonists is a widely used paradigm to induce epileptogenesis in vivo and synchronous activity in brain slices maintained in vitro. However, the mechanisms underlying these effects remain unclear. Here, we used field potential recordings from the lateral entorhinal cortex in horizontal rat brain slices to explore whether two different K(+) currents regulated by muscarinic receptor activation, the inward rectifier (K(IR)) and the M-type (K(M)) currents, have a role in carbachol (CCh)-induced field activity, a prototypical model of cholinergic-dependent epileptiform synchronization. To establish whether K(IR) or K(M) blockade could replicate CCh effects, we exposed slices to blockers of these currents in the absence of CCh. K(IR) channel blockade with micromolar Ba(2+) concentrations induced interictal-like events with duration and frequency that were lower than those observed with CCh; by contrast, the K(M) blocker linopirdine was ineffective. Pre-treatment with Ba(2+) or linopirdine increased the duration of epileptiform discharges induced by subsequent application of CCh. Baclofen, a GABA(B) receptor agonist that activates K(IR), abolished CCh-induced field oscillations, an effect that was abrogated by the GABA(B) receptor antagonist CGP 55845, and prevented by Ba(2+). Finally, when applied after CCh, the K(M) activators flupirtine and retigabine shifted leftward the cumulative distribution of CCh-induced event duration; this effect was opposite to what seen during linopirdine application under similar experimental conditions. Overall, our findings suggest that K(IR) rather than K(M) plays a major regulatory role in controlling CCh-induced epileptiform synchronization.
authors.affiliation: Division of Pharmacology, Department of Neuroscience, School of Medicine, Federico II University of Naples, Naples, Italy. cataldi@unina.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Cataldi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Panuccio
authors.forename: Anna
authors.initials: A
authors.lastname: Cavaccini
authors.forename: Margherita
authors.initials: M
authors.lastname: D'Antuono
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taglialatela
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D011976:Receptors, Muscarinic; D002217:Carbachol