Publication
Title
Involvement of inward rectifier and M-type currents in carbachol-induced epileptiform synchronization
Author
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 (KIR) and the M-type (KM) currents, have a role in carbachol (CCh)-induced field activity, a prototypical model of cholinergic-dependent epileptiform synchronization. To establish whether KIR or KM blockade could replicate CCh effects, we exposed slices to blockers of these currents in the absence of CCh. KIR channel blockade with micromolar Ba2+ concentrations induced interictal-like events with duration and frequency that were lower than those observed with CCh; by contrast, the KM blocker linopirdine was ineffective. Pre-treatment with Ba2+ or linopirdine increased the duration of epileptiform discharges induced by subsequent application of CCh. Baclofen, a GABAB receptor agonist that activates KIR, abolished CCh-induced field oscillations, an effect that was abrogated by the GABAB receptor antagonist CGP 55845, and prevented by Ba2+. Finally, when applied after CCh, the KM 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 KIR rather than KM plays a major regulatory role in controlling CCh-induced epileptiform synchronization.
Language
English
Source (journal)
Neuropharmacology. - Oxford, 1970, currens
Publication
Oxford : 2011
ISSN
0028-3908 [print]
1873-7064 [online]
Volume/pages
60:4(2011), p. 653-661
ISI
000287459600014
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 31.10.2014
Last edited 04.08.2017