Possible mechanism involved in the inhibitory action of U-50, 488H, an opioid kappa agonist, on guinea pig hippocampal CA3 pyramidal neurons in vitro.

Intracellular recordings of the CA3 pyramidal neurons in the guinea pig hippocampus were made in vitro. U-50 488H (100 microM), a selective opioid kappa agonist, decreased the synaptic response produced by stimulation of the mossy fibers but did not affect the membrane potential, the input resistance and the generation of the Na+ spikes or the Ca2+ spikes. Iontophoretically applied U-50 488H depressed the depolarization produced by L-glutamate. U-50 488H (100 microM) also depressed the consistent depolarization produced by veratrine (3 X 10(-5) g/ml) and this effect was partially antagonized by naloxone. Moreover, application of U-50 488H led to a disappearance of the anomalous rectification. These results suggest that U-50 488H depresses the synaptic activities of the CA3 pyramidal neurons by inhibiting a subtype of the Na+ channel, "Na+ channel type II" which slowly closes, of the soma and/or the dendrites of the neurons.