topiramate has been researched along with 1-oleoyl-2-acetylglycerol* in 2 studies
2 other study(ies) available for topiramate and 1-oleoyl-2-acetylglycerol
| Article | Year |
|---|---|
Phosphorylation of sodium channels mediated by protein kinase-C modulates inhibition by topiramate of tetrodotoxin-sensitive transient sodium current.
Topiramate is a novel anticonvulsant known to modulate the activity of several ligand- and voltage-gated ion channels in neurons. The mechanism of action of topiramate, at a molecular level, is still unclear, but the phosphorylation state of the channel/receptor seems to be a factor that is able to influence its activity. We investigated the consequences of phosphorylation of the sodium channel on the effect of topiramate on tetrodotoxin (TTX)-sensitive transient Na(+) current (I(NaT)).. I(NaT) was recorded in dissociated neurons of rat sensorimotor cortex using whole-cell patch-clamp configuration.. We found that topiramate (100 microM) significantly shifted the steady-state I(NaT) inactivation curve in a hyperpolarized direction. In neurons pre-treated with a PKC-activator, 1-oleoyl-2-acetyl-sn-glycerol (OAG; 2 microM), the net effect of topiramate on steady-state I(NaT) inactivation was significantly decreased. In addition, OAG also slightly shifted the I(NaT) activation curve in a hyperpolarized direction, while perfusion with topiramate had no effect on the parameters of I(NaT) activation.. These data show that PKC-activation can modulate the effect of topiramate on I(NaT). This suggests that channel phosphorylation in physiological or pathological conditions (such as epiliepsy), can alter the action of topiramate on sodium currents. Topics: Animals; Anticonvulsants; Brain; Diglycerides; Fructose; In Vitro Techniques; Membrane Potentials; Motor Cortex; Patch-Clamp Techniques; Phosphorylation; Protein Kinase C; Rats; Rats, Sprague-Dawley; Sodium Channels; Tetrodotoxin; Topiramate | 2007 |
Protein-kinase C-dependent phosphorylation inhibits the effect of the antiepileptic drug topiramate on the persistent fraction of sodium currents.
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. Topics: Action Potentials; Animals; Anticonvulsants; Cell Membrane; Cells, Cultured; Cerebral Cortex; Diglycerides; Enzyme Activators; Fructose; Neurons; Patch-Clamp Techniques; Phosphorylation; Protein Kinase C; Rats; Rats, Sprague-Dawley; Sodium Channels; Topiramate | 2004 |