Different responses to opioids measured in terminals and somas of Edinger-Westphal neurons

Abstract

Neurotransmitter receptors on the axon terminals of a neuron can be located a considerable distance away from comparable receptors on the cell body or dendrites of the same neuron. We examined the effects of activating either nerve terminal receptors or those located on or near the somas of chick Edinger-Westphal neurons. Cell body responses were measured via intracellular recording in a brain slice preparation. To measure nerve terminal responses, intracellular recordings were obtained from the large, calyciform nerve endings in intact ciliary ganglia, which emanate from neurons of the lateral Edinger-Westphal nucleus. Cell bodies of Edinger-Westphal neurons responded to leucine-enkephalin with a dose-dependent hyperpolarization that was associated with a decrease in input resistance. In spontaneously active Edinger-Westphal somas, leucine-enkephalin caused marked inhibition of suprathreshold and subthreshold activity, indicating that, as with a number of other central neurons, the major effect of opioids was to reduce excitability. The response to opioids was sensitive to naloxone (1 μM) and was a direct effect, since it was not blocked by either 0.5 μM tetrodotoxin or 100 μM cadmium. More selective mu ([ d-Ala 2, N-Me-Phe 4, Gly 5-ol]-enkephalin) and delta ([ d-Ser 2]-leucine-enkephalin-Thr and [ d-Pen 2,5]-enkephalin) opioid agonists produced effects similar to those of leucine-enkephalin. Opioids produced strikingly different effects in the nerve terminals of Edinger-Westphal neurons, where the major effect was a depolarization associated with a decrease in input resistance. The effects of opioids in the terminals were reduced in a low sodium buffer, indicating that they were dependent on the presence of extracellular sodium. In contrast, altering extracellular potassium or calcium had little effect on the response. The actions of the tachykinin peptide substance P were also examined in both preparations. Substance P elicited similar responses in both terminals and cell bodies of Edinger-Westphal neurons. These responses consisted of a membrane depolarization associated with little or no change in input resistance and increased cell excitability. The present results indicate that in at least one type of vertebrate neuron, opioid receptors exert different actions depending upon their localization within the neuron. Since opioid receptors are dependent on coupling to G-proteins to elicit effects on membrane-spanning ion channels, it thus appears that neurotransmitter receptors can be functionally coupled to different ion channels within the same neuron.