Opiates and enkephalin reduce the excitability of neuronal processes

Abstract

Intracellular recordings were made from somata of neurones in the myenteric ganglia of ileum isolated from guinea-pigs. Action potentials were evoked in the soma either by stimulating a cell process at a distance of up to 100 μm from the soma, and allowing the spike to propagate along the process, or by directly depolarizing the soma membrane by passing current through the recording electrode. Enkephalin, morphine and levorphanol prevented the appearance in the soma of the action potential following distant stimulation, without changing the action potential caused by direct depolarization of the neuron soma. This occurred whether these substances were applied by superfusion (100 nM-1 μM) or by electrophoresis; however, electrophoretic application was usually more effective when the tip of the electrophoresis electrode was close to the course of the cell process. These effects were not shared by dextrorphan, and were prevented by naloxone (100 nM-1 μM). The opiates and enkephalin sometimes caused the action potential to fractionate, suggesting that an important site of action in many neurones may be the proximal part of the process. The block of action potential propagation which occurred at the proximal process, or more distal parts of the process, was sometimes but usually not associated with a hyperpolarization of the membrane of the soma. The results indicate that opiates and enkephalin either block action potential propagation along, or initiation in, fine unmyelinated varicose processes in neurons in which they have no detectable effects on soma membrane properties. The mechanism of spike blockade may be local hyperpolarization or conductance increase.