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

Abstract

Intracellular recordings of the CA3 pyramidal neurons in the guinea pig hippocampus were made in vitro. U-50 488H (100 μM), a selective opioid κ 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 μM) also depressed the consistent depolarization produced by veratrine (3×10^-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.