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

¹Department of Physiology and Pharmacology and ²Department of Neurology, State University of New York Downstate Medical Center, Brooklyn, New York

Submitted 25 May 2005; accepted in final form 21 July 2005

Activation 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 protein 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 µM picrotoxin, a -aminobutyric acid type A antagonist, 250- to 500-ms synchronized bursts were elicited. (S)-3,5-Dihydroxyphenylglycine (DHPG, 50 µM), 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 µM chelerythrine, a PKC inhibitor, indicating that DHPG-induced epileptogenesis is PKC independent. However, although PLD activation with CSA (100 µM) 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 CSA-mediated 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.

This article has been cited by other articles:

				A. Kumar and T. C. Foster Shift in Induction Mechanisms Underlies an Age-Dependent Increase in DHPG-Induced Synaptic Depression at CA3 CA1 Synapses J Neurophysiol, November 1, 2007; 98(5): 2729 - 2736. [Abstract] [Full Text] [PDF]