Title

Action of κ and Δ opioid agonists on premotor cardiac vagal neurons in the nucleus ambiguus

Document Type

Journal Article

Publication Date

10-25-2004

Journal

Neuroscience

Volume

129

Issue

1

DOI

10.1016/j.neuroscience.2004.07.021

Keywords

ambiguus; bradycardia; parasympathetic

Abstract

Both enkephalin and dynorphin containing fibers are in close proximity to neurons in the nucleus ambiguus, including cardiac vagal neurons. Microinjection of Δ and κ agonists into the nucleus ambiguus have been shown to evoke decreases in heart rate. Yet little is known about the mechanisms by which Δ and κ opioid receptors alter the activity of cardiac vagal neurons. This study tests whether κ and Δ opioid agonists can alter the activity of cardiac vagal neurons by modulating likely opioid targets including voltage gated calcium currents, and both glycinergic and GABA) neurotransmission to cardiac vagal neurons. Cardiac vagal neurons were identified in vitro by a fluorescent tracer and studied using patch clamp techniques. Neither the κ agonist spiradoline or the Δ agonist [D-Pen 2, D-Pen 5]enkephalin (DPDPE) modulated the voltage gated calcium currents in cardiac vagal neurons. DPDPE also did not alter either glycinergic or GABAergic synaptic neurotransmission. Spiradoline did not change GABAergic synaptic inputs, but did significantly inhibit glycinergic synaptic inputs to cardiac vagal neurons. At a concentration of 1 μM, spiradoline inhibited the amplitude of glycinergic events, and at a concentration of 5 μM, spiradoline inhibited both glycinergic amplitude and frequency. Spiradoline also inhibited both the amplitude and frequency of glycinergic miniature inhibitory post-synaptic currents,indicating κ agonists likely act at both presynaptic and postsynaptic sites to inhibit glycinergic neurotransmission to cardiac vagal neurons. © 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

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