Valproate reduced synaptic activity increase induced by 4-aminopyridine at the hippocampal CA3-CA1 synapse.
OBJECTIVE
We investigated the effects of valproate (VPA) on excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP) to determine whether the antiepileptic effects shown by VPA can be ascribed to a modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in the CA3-CA1 synapse.


METHODS
Rat hippocampal slices were prepared and maintained in vitro with standard methods. Whole-cell current and voltage-clamp recordings were obtained from CA1 pyramidal neurons by using the "blind" patch-clamp technique in an immersion recording chamber. Increase in the spontaneous excitatory synaptic activity was induced by addition of 4-AP to the medium.


RESULTS
Perfusion with VPA significantly counteracted the increase of frequency and amplitude of the sEPSCs induced by application of 4-AP and suppressed the epileptiform activity.


CONCLUSIONS
We conclude that VPA decreases the 4-AP-induced enhancement of excitatory synaptic activity at the CA3-CA1 synapse, and that this reduction of excitation input to CA1 contributes to the anticonvulsant effects of VPA.
Martín
Eduardo D
ED
Brain Mapping Unit, Pluridisciplinary Institute, UCM, Madrid, Spain. eduardo.martin@uclm.es
Pozo
Miguel A
MA
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004336:Drug Antagonism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D026902:Potassium Channel Blockers; D014635:Valproic Acid; D015761:4-Aminopyridine