title: Microinjection of kynurenic acid in the rostral nucleus of the tractus solitarius disrupts spatiotemporal aspects of mechanically induced tracheobronchial cough.
abstract: The importance of neurons in the nucleus of the solitary tract (NTS) in the production of coughing was tested by microinjections of the nonspecific glutamate receptor antagonist kynurenic acid (kyn; 100 mM in artificial cerebrospinal fluid) in 15 adult spontaneously breathing anesthetized cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airway. Electromyograms (EMG) were recorded from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles. Bilateral microinjections of kyn into the NTS rostral to obex [55 ± 4 nl total in 2 locations (n= 6) or 110 ± 4 nl total in 4 locations (n= 5)], primarily the ventrolateral subnucleus, reduced cough number and expiratory cough efforts (amplitudes of ABD EMG and maxima of esophageal pressure) compared with control. These microinjections also markedly prolonged the inspiratory phase, all cough-related EMG activation, and the total cough cycle duration as well as some other cough-related time intervals. In response to microinjections of kyn into the NTS rostral to the obex respiratory rate decreased, and there were increases in the durations of the inspiratory and postinspiratory phases and mean blood pressure. However, bilateral microinjections of kyn into the NTS caudal to obex as well as control vehicle microinjections in the NTS location rostral to obex had no effect on coughing or cardiorespiratory variables. These results are consistent with the existence of a critical component of the cough rhythmogenic circuit located in the rostral ventral and lateral NTS. Neuronal structures of the rostral NTS are significantly involved specifically in the regulation of cough magnitude and phase timing.NEW & NOTEWORTHYThe nucleus of the solitary tract contains significant neuronal structures responsible for control of1) cough excitability,2) motor drive during cough,3) cough phase timing, and4) cough rhythmicity. Significant elimination of neurons in the solitary tract nucleus results in cough apraxia (incomplete and/or disordered cough pattern). The mechanism of the cough impairment is different from that for the concomitant changes in breathing.
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.|Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.
authors.forename: Ivan
authors.initials: I
authors.lastname: Poliacek
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.|Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Teresa
authors.identifier: 0000-0001-9448-2175
authors.initials: T
authors.lastname: Pitts
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Rose
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Davenport
authors.affiliation: Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.
authors.forename: Michal
authors.initials: M
authors.lastname: Simera
authors.affiliation: Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.
authors.forename: Marcel
authors.initials: M
authors.lastname: Veternik
authors.affiliation: Institute of Medical Biophysics, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic; and.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kotmanova
authors.affiliation: Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida; bolser@ufl.edu.
authors.forename: Donald C
authors.initials: DC
authors.lastname: Bolser
mesh_terms: D000009:Abdominal Muscles / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002415:Cats; D003371:Cough / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D010507:Periodicity; D010812:Physical Stimulation; D012119:Respiration / Q000187:drug effects; D012132:Respiratory Muscles / Q000187:drug effects / Q000503:physiopathology; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007736:Kynurenic Acid
keywords: abdominal muscle activity; cough; cough phase timing; kynurenate; nucleus of solitary tract