Protein-kinase C-dependent phosphorylation inhibits the effect of the antiepileptic drug topiramate on the persistent fraction of sodium currents

Neuroscience
G CuriaS Franceschetti

Abstract

We investigated the interference of protein-kinase C (PKC)-dependent Na(+) channel phosphorylation on the inhibitory effect that the antiepileptic drug topiramate (TPM) has on persistent Na(+) currents (I(NaP)) by making whole cell patch-clamp and intracellular recordings of rat sensorimotor cortex neurons. The voltage-dependent activation of I(NaP) was significantly shifted in the hyperpolarizing direction when PKC was activated by 1-oleoyl-2-acetyl-sn-glycerol (OAG). TPM reduced the peak amplitude of I(NaP), but it did not counteract the OAG-induced shift in I(NaP) activation. Firing property experiments showed that the firing threshold was lowered by OAG. TPM was unable to counteract this effect, which may be due to OAG-dependent enhancement of the contribution of subthreshold I(NaP). These data suggest that PKC activation may limit the effect of the anticonvulsant TPM on the persistent fraction of Na(+) currents. The channel phosphorylation that may occur in cortical neurons as a result of physiological or pathological (e.g. epileptic) events can modulate the action of TPM on Na(+) currents.

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Citations

Sep 11, 2012·Brain : a Journal of Neurology·Niels EijkelkampJohn N Wood
Feb 24, 2007·Epilepsia·Heinz Beck
Jul 16, 2008·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Minoru KobayashiJoji Nakamura
Jan 18, 2014·Current Medical Research and Opinion·Natalia Paola CatoiraClaudio Gonzalez
May 19, 2009·Pharmacology, Biochemistry, and Behavior·Scott M RawlsRobert B Raffa
May 17, 2008·CNS Neuroscience & Therapeutics·Richard P Shank, Bruce E Maryanoff
Sep 6, 2005·Brain Research Bulletin·Valéria KecskemétiGéza Szûcs
Jun 24, 2010·Early Human Development·Dorottya Kelen, Nicola J Robertson
Dec 1, 2005·Brain : a Journal of Neurology·Stefan Remy, Heinz Beck
Feb 10, 2006·Journal of Neurophysiology·P AracriS Franceschetti
Apr 17, 2014·The Journal of Biological Chemistry·Je-Hyun BaekJames S Trimmer
Dec 3, 2016·Headache·Stephen D Silberstein

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