EFFECTS OF CONVULSANT AND ANTICONVULSANT DRUGS ON VOLTAGE-OPERATED AND LIGAND-OPERATED ION CHANNELS

The injection of mRNA from rats' brains into the oocytes of Xenopus la evis led to the expression of the voltage operated potassium channel K v1.1 and the ligand operated ion channels sensitive to the following l igands: gamma-aminobutyric acid (GABA), the glutamate agonists N-methy l-D-aspartate (NMDA), kainate (KA), lpha-amino-3-hydroxy-5-methyl-4-is oxazolpropionate (AMPA) and quisqualate (QA). The effects of the convu lsant pentylenetetrazol (PTZ) on the voltage operated ion channel and of the anticonvulsant valproic acid (VPA) on the ligand operated ion c hannels were investigated. The Kv1.1 channel was affected by PTZ in a voltage-dependent manner. PTZ increased the potassium currents at more negative potentials and decreased them at more positive potentials. T he membrane currents were increased at a potential of -50 mV by 97% an d were decreased at -20 mV by 20% of the control value. This effect of PTZ represents a ''discriminatory function'' that may contribute to e pileptogenesis in nervous tissue. The anticonvulsant VPA did not influ ence membrane currents induced by the GABA(A) operated ion channels. M embrane currents of the glutamate receptor subtypes were affected by V PA in a different manner. VPA reduced membrane currents elicited by NM DA by 15%, and increased KA-induced membrane currents by 7% of the con trol value. Membrane currents elicited by AMPA and QA were not affecte d by the anticonvulsant substance. The reducing effect on the NMDA-ind uced membrane currents may contribute to the antiepileptic action of V PA.