Blockade of gamma-aminobutyric acid-gated chloride current in frog sensory neurons by picrotoxin.

The mechanism of picrotoxin (PTX) suppression of the gamma-aminobutyric acid (GABA)-gated Cl- current (ICl) was examined in frog sensory neurons using the 'concentration-clamp' technique. The activation phase of GABA-induced ICl showed little change with the concomitant application of 10(-5) M PTX; however, the inactivation phase was markedly facilitated. ICl produced by simultaneous application of GABA and PTX was non-competitively suppressed while the plateau current showed a mixed type of competitive and non-competitive inhibitions. When the neuron was pretreated with PTX, the peak current of ICl produced by the simultaneous application of PTX and GABA was gradually suppressed, but the suppression of plateau level of ICl was rapid and not affected by pretreatment time. Recovery was not influenced by the length of pretreatment but depended only slightly on wash time. A major part of recovery occurred through the reactivation of the inhibited GABA receptor-ionophore complex by GABA. The first application of 3 x 10(-6) M GABA, after the response to 3 x 10(-6) M GABA was suppressed by the concomitant application of PTX, produced ICl consisting of the rapid phase and the slowly developing phase. ICl produced by simultaneous application of 10(-5) M GABA and 10(-5) M PTX and by the first application of 10(-5) M GABA after the inhibition showed a similar voltage dependence to the control ICl. These results indicate that PTX has access to the binding site inside the Cl- channel either through open channels or with different efficacies through closed channels, and thereby inhibits the GABA response by modifying the gating process.