title: Ancient gill and lung oscillators may generate the respiratory rhythm of frogs and rats.
abstract: Though the mechanics of breathing differ fundamentally between amniotes and "lower" vertebrates, homologous rhythm generators may drive air breathing in all lunged vertebrates. In both frogs and rats, two coupled oscillators, one active during the inspiratory (I) phase and the other active during the preinspiratory (PreI) phase, have been hypothesized to generate the respiratory rhythm. We used opioids to uncouple these oscillators. In the intact rat, complete arrest of the external rhythm by opioid-induced suppression of the putative I oscillator, that is, pre-Bötzinger complex (PBC) oscillator, did not arrest the putative PreI oscillator. In the unanesthetized frog, the comparable PreI oscillator, that is, the putative buccal/gill oscillator, was refractory to opioids even though the comparable I oscillator, the putative lung oscillator, was arrested. Studies in en bloc brainstem preparations derived from both juvenile frogs and metamorphic tadpoles confirmed these results and suggested that opioids may play a role in the clustering of lung bursts into episodes. As the frog and rat respiratory circuitry produce functionally equivalent motor outputs during lung inflation, these data argue for a close homology between the frog and rat oscillators. We suggest that the respiratory rhythm of all lunged vertebrates is generated by paired coupled oscillators. These may have originated from the gill and lung oscillators of the earliest air breathers.
authors.affiliation: Department of Medicine, University of Calgary, 3330 Hospital Drive, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Konstantinon
authors.initials: K
authors.lastname: Vasilakos
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Wilson
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kimura
authors.forename: John E
authors.initials: JE
authors.lastname: Remmers
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001683:Biological Clocks; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology; D005880:Gills / Q000187:drug effects / Q000502:physiology*; D006935:Hypercapnia / Q000503:physiopathology; D066298:In Vitro Techniques; D007814:Larva / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009415:Nerve Net / Q000033:anatomy & histology; D010507:Periodicity; D017156:Photoplethysmography / Q000379:methods; D010805:Physical Conditioning, Animal; D011898:Ranidae; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012143:Respiratory Physiological Phenomena; D014628:Vagotomy / Q000379:methods
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D005283:Fentanyl