Contrasting Roles of Protein Kinase C in Induction Versus Suppression of Group I mGluR-Mediated Epileptogenesis In Vitro

John C. Cuellar, Elvin L. Griffith, Lisa R. Merlin
2005 Journal of Neurophysiology  
Contrasting roles of protein kinase C in induction versus suppression of group I mGluR-mediated epileptogenesis in vitro. tion of group I metabotropic glutamate receptors (mGluRs) elicits persistent ictaform discharges in guinea pig hippocampal slices, providing an in vitro model of epileptogenesis. The induction of these persistent ictaform bursts is prevented by L-cysteine sulfinic acid (CSA), an agonist at phospholipase D (PLD)-coupled mGluRs. Studies described herein examined the role of
more » ... tein kinase C (PKC) in both the group I mGluR-mediated induction and CSA-mediated suppression of this form of epileptogenesis. Intracellular recordings were performed from CA3 stratum pyramidale and synchronized burst length was monitored. In the presence of 50 M picrotoxin, a ␥-aminobutyric acid type A antagonist, 250-to 500-ms synchronized bursts were elicited. (S)-3,5-Dihydroxyphenylglycine (DHPG, 50 M), an agonist at group I mGluRs, increased the burst length to 1-3 s in duration, a change that persisted after agonist washout. This persistent change in burst length was elicited in the presence of 10 M chelerythrine, a PKC inhibitor, indicating that DHPG-induced epileptogenesis is PKC independent. However, although PLD activation with CSA (100 M) was highly effective at suppressing group I mGluR-mediated induction of burst prolongation, CSA application in the presence of chelerythrine was no longer effective and resulted in the expression of persistent ictaform bursts. These data suggest that CSAmediated suppression of group I mGluR-induced epileptogenesis is PKC dependent. We propose that CSA mediates its effect by PLD-driven activation of PKC, which may desensitize the phospholipase C-linked group I mGluRs and thereby prevent group I mGluR-induced epileptogenesis.
doi:10.1152/jn.00548.2005 pmid:16049142 fatcat:tpcxmxals5g3ldzia5v6a6ec6q