title: Electrophysiological demonstration and activation of mu-opioid receptors in the rabbit sinoatrial node.
abstract: To investigate the presence of opioid receptors and their physiological role in cardiac pacemaker cells, we studied electrophysiological effects of fentanyl citrate, an activator of the mu-opioid receptors, on the spontaneous action potential (AP) and membrane currents, using small preparations (0.2 x 0.2 x 0.1 mm) of rabbit sinoatrial (SA) node (SAN). Fentanyl (0.1-3 microM) progressively decreased the AP amplitude (APA), maximal rate of depolarization (MRD), and spontaneous firing frequency (SFF) and prolonged the AP duration (APD) and diastolic interval in a concentration-dependent manner. At 1 microM, the spontaneous activity ceased in two of the eight preparations. These actions were blocked by a mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), but were not modified by either kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), or delta-opioid receptor antagonist ICI-174864. In voltage-clamp experiments using double microelectrode techniques, 1 microM fentanyl reduced the Ca2+ current (ICa) obtained on step depolarization from -40 to 0 mV by 19.9 +/- 9.3% (p < 0.05, n = 5), the fast and slow components of the delayed rectifying K+ current (IKfast, IKslow) tail obtained on repolarization from 10 to -60 mV by 54.7 +/- 4.7 and 41.4 +/- 2.4% (p < 0.05, n = 4), and the hyperpolarization-activated inward current at -90 mV by 12.6 +/- 0.5% (p < 0.05, n = 7), respectively. The gating kinetics of ICa and IKslow were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Cardiovascular Institute, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saeki
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Fujinami
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D008839:Microelectrodes; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D005283:Fentanyl