The effects of the muscle relaxant, CS-722, on synaptic activity of cultured neurones.

1. The pharmacological properties of the centrally acting muscle relaxant, CS-722, were studied in cultured hippocampal cells and dorsal root ganglion cells of the rat using the whole-cell variation of the patch clamp technique. 2. CS-722 inhibited the occurrence of spontaneous excitatory and inhibitory postsynaptic currents in hippocampal neurones at concentrations of 100-300 microM, but had no effect on postsynaptic currents evoked by the application of glycine, gamma-aminobutyric acid, glutamate or N-methyl-D-aspartate. 3. CS-722 reduced voltage-gated sodium currents, while shifting the sodium channel inactivation curve to more negative membrane potentials. This effect is similar to that reported for local anaesthetics. Voltage-gated potassium currents were decreased by CS-722 by approximately 20%, whereas voltage-activated calcium currents were inhibited by about 25%. 4. CS-722 inhibited evoked inhibitory postsynaptic currents. However, the spontaneous quantal release of inhibitory transmitter was not affected. 5. The inhibitory effect of CS-722 on spontaneous inhibitory postsynaptic currents and excitatory postsynaptic currents in hippocampal cultures probably results from an inhibition of both sodium and calcium currents. This inhibitory effect is likely to be amplified in polysynaptic neuronal circuits.