The actions of the κ1 opioid agonist U-50,488 on presynaptic nerve terminals of the chick ciliary ganglion

Abstract

The actions of the κ 1 opioid receptor agonist U-50,488 ( trans-(±)-3,4-dichloro- N-methyl- N-[2-(1-pyrrolidinyl) cyclohexyr]-benzene-acetamide methane sulfonate) on the membrane properties of presynaptic calyciform nerve terminals of the chick ciliary ganglion were examined using intracellular recordings obtained from intact ganglion preparations maintained in vitro. U-50,488 produced a concentrationdependent (30–1000 μM) hyperpolarization with an apparent increase in input resistance. This hyperpolarization resulted from inhibition of the Na +-K + inward rectifier, since it was blocked by 3 mM Cs + and was not observed when terminals were depolarized beyond resting potential where inward rectification was voltage inactivated. A depolarizing effect on membrane potential with a further rise in input resistance was commonly observed at the highest perfused U-50,488 concentration (1 mM). The depolarizing event appears to result from a decrease in membrane potassium conductance, as the reversal potential for the response was estimated to be between −70 and −90 mV and the potassium channel blocker Ba 2+ (1mM) abolished the response. The κ 1 opioid receptor agonist also blocked spontaneously occurring miniature hyperpolarizations in the terminals, which are considered to be due to a Ca 2+-dependent K + conductance. Most of the responses to U-50,488 were abolished in the presence of the κ 1 receptor antagonist norbinaltorphimine. In conclusion, the excitability of presynaptic nerve terminals in the chick ciliary ganglion can be modulated by the inhibition of at least three separate ion conductances following activation of κ 1 opioid receptor sites in the nerve terminal region.