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Am J Physiol Heart Circ Physiol 274: H441-H447, 1998;
0363-6135/98 $5.00
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Vol. 274, Issue 2, H441-H447, February 1998

Localization and functional effects of adenosine A1 receptors on cardiac vagal afferents in adult rats

Holly R. Middlekauff1, Scott A. Rivkees2, Helen E. Raybould3, Melo Bitticaca1, Joshua I. Goldhaber1, and James N. Weiss1

1 Division of Cardiology, University of California Los Angeles School of Medicine, 3 Department of Physiological Science, University of California, Los Angeles, California 90095; and 2 Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520

There is evidence to suggest that during ischemia adenosine acts on cardiac vagal afferent neurons to activate systemic reflexes and to modulate cardiac nociception. The purpose of this study was to determine whether adenosine receptors are present and have direct cellular electrophysiological actions on cardiac vagal afferent neurons. In radioreceptor assays of nodose ganglion tissue from rats, binding was detectable for A1 (39.6 ± 1.2 fmol/mg protein) but not A2a adenosine receptors. These findings were confirmed using the complementary approach of receptor-labeling autoradiography. Using in situ hybridization, we saw specific labeling over ~50% of neurons in the nodose ganglia, but not over nonneuronal cells. In colabeling studies, cardiac vagal afferent neurons were identified by retroneuronal labeling with fluororuby. Of cardiac vagal afferents approximately one-half were strongly positive for A1 adenosine receptors (immunocytochemistry). In patch-clamping experiments, adenosine inhibited peak inward calcium current in 7 of 11 cells by 48 ± 13%. In conclusion, adenosine A1 receptors reside on a subset of vagal afferent neurons, including cardiac vagal afferents, and have electrophysiological effects that modulate neuroexcitability in cultured nodose ganglion neurons.

nodose ganglion; retroneuronal labeling; ion channels


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