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.
|Data di pubblicazione:||2002|
|Autore/i:||Aracri P; Curia G; Sancini G; Franceschetti S; Spreafico R; Mantegazza M; Avanzini G|
|Titolo:||PKC-dependent channel phosphorylation modulates the effect of the anticonvulsant topiramate (TPM) on sodium current.|
|Nome del convegno:||Society for Neuroscience, 32nd Annual Meeting|
|Luogo del convegno:||Orlando, Florida, USA|
|Data del convegno:||November 2-7, 2002|
|Citazione:||PKC-dependent channel phosphorylation modulates the effect of the anticonvulsant topiramate (TPM) on sodium current. / Aracri P; Curia G; Sancini G; Franceschetti S; Spreafico R; Mantegazza M; Avanzini G. - (2002). ((Intervento presentato al convegno Society for Neuroscience, 32nd Annual Meeting tenutosi a Orlando, Florida, USA nel November 2-7, 2002.|
|Tipologia||Abstract in Atti di Convegno|
File in questo prodotto:
I documenti presenti in Iris Unimore sono rilasciati con licenza Creative Commons Attribuzione - Non commerciale - Non opere derivate 3.0 Italia, salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris