Convulsant-induced depression of amino acid responses in cultured mouse spinal neurones studied under voltage clamp

Abstract

1 A two-microelectrode voltage-clamp technique was used to record membrane current responses induced by the application of the neutral amino acids, γ-aminobutyric acid (GABA) and glycine, to mouse spinal neurones maintained in cell culture. 2 Membrane current responses to GABA were depressed by the convulsant agents, bicuculline, Picrotoxin and pentylenetetrazole. Membrane current responses to glycine were depressed by the convulsant compound, strychnine. 3 Analysis of the fluctuations in membrane current about the mean response during prolonged applications of GABA revealed that neither the conductance nor the average open-time of GABA-activated ion-channels was altered in the presence of Picrotoxin or bicuculline. Pentylenetetrazole caused a reduction in the open-time of GABA-activated ion-channels but this effect alone was too small to account for the depression of the current response. 4 A similar analysis of glycine-induced responses in the presence of strychnine revealed that the depression of glycine responses by strychnine was not associated with any changes in the conductance or average open-time of glycine-activated ion-channels. 5 We therefore conclude that the convulsant compounds act by reducing the rate of activation of ion-channels by the neutral amino acids either through a reduction in the number of free receptors or by a change in the kinetics of channel activation.