Valproate selectively reduces the persistent fraction of Na+ current in neocortical neurons.
The effect of valproate (VPA) on Na+ currents (INa), was studied by means of voltage clamp recordings using whole-cell patch clamp configuration in 21 acutely dissociated neocortical neurons. Concentrations of VPA up to 200 microM failed to induce any detectable decrease in fast INa (I(Naf)), but the persistent fraction (I(NaP)) was significantly reduced by low VPA concentrations (10-30 microM), corresponding to the lower values of the 'therapeutic' range in epileptic patients. Since it is known that I(NaP) critically regulates the firing properties of pyramidal neurons, it is suggested that the anticonvulsant effectiveness of VPA is mainly due to its effect on I(NaP).
Istituto Nazionale Neurologico C. Besta, Laboratorio di Neurofisiologia Sperimentale, Milano, Italy.
S
S
Taverna
M
M
Mantegazza
S
S
Franceschetti
G
G
Avanzini
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D002478:Cells, Cultured; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D019579:Neocortex / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D000927:Anticonvulsants; D015222:Sodium Channels; D014635:Valproic Acid