Bicuculline and its methochloride salt block inhibitory postsynaptic potentials recorded from giant interneurone 2 (GI 2) of the cockroach Periplaneta americana following stimulation of cercal nerve X, but fail to block the response to gamma-aminobutyric acid (GABA) when this neurotransmitter is ionophoresed or pressure-injected onto the fine branches of GI 2 within the neuropile of the terminal abdominal ganglion. Bicuculline is similarly ineffective in blocking the response recorded when GABA is ionophoresed onto the cell body membrane of GI 2. The cell body membranes of cockroach GI 2 and fast coxal depressor motor neurones have been used to show that bicuculline blocks cell body (extrasynaptic) neuronal nicotinic acetylcholine receptors. Pressure-injection of acetylcholine into the neuropile results in a depolarization of GI 2 that is blocked by bicuculline. Therefore, the block by bicuculline of inhibitory postsynaptic potentials recorded from GI 2 may result in part from actions at sites other than synaptic GABA receptors. Alternatively, there may exist a population of synaptic GABA receptors on GI 2 that, unlike GI 2 cell body GABA receptors, are sensitive to bicuculline.

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