Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle

Victor Ruiz-Velasco, Henry L. Puhl, Brad C. Fuller, Andrew D. Sumner

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Postganglionic sympathetic nerve terminals innervate cardiac muscle and express opioid receptor-like 1 (ORL1) receptors, the most recently described member of the opioid receptor subclass. ORL1 receptors are stimulated by the endogenous heptadecapeptide nociceptin (Noc). To better understand how the signaling events by Noc regulate sympathetic neuron excitability, the goal of the present study was to determine whether sympathetic stellate ganglion (SG) neurons, innervating the heart, natively express ORL1 opioid receptors and couple to Ca2+ channels. SG neurons in adult male rats were retrograde-labeled with a fluorescent tracer via injection of the ventricular muscle employing ultrasound imaging. Thereafter, N-type Ca2+ channel modulation was investigated using the whole-cell variant of the patch-clamp technique. Exposure of labeled SG neurons to Noc resulted in a concentration-dependent inhibition of Ca2+ currents (with an estimated EC50 of 193 ± 14 nM). Pre-exposure of SG neurons to the ORL1 receptor blocker, [Nphe1,Arg14,Lys 15]N/OFQ-NH2 (UFP-101), significantly decreased the Noc-mediated Ca2+ current inhibition. The Ca2+ current inhibition was also blocked by pertussis toxin pretreatment, indicating that signaling occurs via Gαi/o G proteins. Finally, the full-length ORL1 receptor cDNA in SG neurons was cloned and sequenced. Of the two known alternatively spliced variants in rats, sequencing analysis showed that the ORL1 receptor expressed in SG neurons is the short form. Overall, these results suggest that stimulation of postsynaptic ORL1 receptors by Noc in SG neurons regulate cardiac sympathetic activity.

Original languageEnglish (US)
Pages (from-to)987-994
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume314
Issue number3
DOIs
StatePublished - Sep 1 2005

Fingerprint

Stellate Ganglion
Opioid Receptors
Myocardium
Neurons
Gi-Go GTP-Binding Protein alpha Subunits
Sympathetic Ganglia
Pertussis Toxin
Patch-Clamp Techniques
Ultrasonography
Complementary DNA
Muscles

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle",
abstract = "Postganglionic sympathetic nerve terminals innervate cardiac muscle and express opioid receptor-like 1 (ORL1) receptors, the most recently described member of the opioid receptor subclass. ORL1 receptors are stimulated by the endogenous heptadecapeptide nociceptin (Noc). To better understand how the signaling events by Noc regulate sympathetic neuron excitability, the goal of the present study was to determine whether sympathetic stellate ganglion (SG) neurons, innervating the heart, natively express ORL1 opioid receptors and couple to Ca2+ channels. SG neurons in adult male rats were retrograde-labeled with a fluorescent tracer via injection of the ventricular muscle employing ultrasound imaging. Thereafter, N-type Ca2+ channel modulation was investigated using the whole-cell variant of the patch-clamp technique. Exposure of labeled SG neurons to Noc resulted in a concentration-dependent inhibition of Ca2+ currents (with an estimated EC50 of 193 ± 14 nM). Pre-exposure of SG neurons to the ORL1 receptor blocker, [Nphe1,Arg14,Lys 15]N/OFQ-NH2 (UFP-101), significantly decreased the Noc-mediated Ca2+ current inhibition. The Ca2+ current inhibition was also blocked by pertussis toxin pretreatment, indicating that signaling occurs via Gαi/o G proteins. Finally, the full-length ORL1 receptor cDNA in SG neurons was cloned and sequenced. Of the two known alternatively spliced variants in rats, sequencing analysis showed that the ORL1 receptor expressed in SG neurons is the short form. Overall, these results suggest that stimulation of postsynaptic ORL1 receptors by Noc in SG neurons regulate cardiac sympathetic activity.",
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Modulation of Ca2+ channels by opioid receptor-like 1 receptors natively expressed in rat stellate ganglion neurons innervating cardiac muscle. / Ruiz-Velasco, Victor; Puhl, Henry L.; Fuller, Brad C.; Sumner, Andrew D.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 314, No. 3, 01.09.2005, p. 987-994.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Ruiz-Velasco, Victor

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