Specific subnuclei of the nucleus tractus solitarius play a role in determining the duration of inspiration in the rat.
Our previous data obtained in the cat suggest that the neurons of the ventrolateral subnucleus of the tractus solitarius (vlNTS) act as an inspiratory off-switch and terminate the inspiratory phase of the respiratory cycle (Berger et al., Eur. J. Pharmacol. 277 (1995) 195-208; Gillis et al., Neurosci. Abstr. 23 (1997) 725). The purpose of the present study was to determine whether inhibition of the region of the vlNTS of the rat using drugs that hyperpolarize, disfacilitate or block both axonal conduction and action potential generation would alter the inspiratory phase of the respiratory cycle. Experiments were conducted in anesthetized, vagotomized and spontaneously breathing rats while monitoring diaphragmatic electromyogram activity. Vagus nerves were sectioned in order to rule out prolongation of inspiration evoked by microinjection of agents into the vlNTS which block excitatory drive from lung afferent inputs. Bilateral microinjection of the inhibitory amino acid gamma-aminobutyric acid (GABA) 25 nmol/45 nl produced an immediate prolongation of inspiratory duration (484+/-18 to 1291+/-84 ms) and an apneustic pattern of breathing. Other effects observed were a significant shortening of expiratory duration (778+/-36 to 432+/-38 ms), rise in blood pressure (83+/-4 to 108+/-6 mmHg) and a small but significant increase in heart rate (439+/-17 to 452+/-18 beats/min). Bilateral microinjection of the ionotropic glutamate receptor antagonist kynurenic acid (1 nmol) and the Na(+) channel blocker tetrodotoxin (10 pmol) into the region of the vlNTS consistently produced a similar prolongation of inspiratory duration and an apneustic pattern of breathing. These results support the hypothesis that neurons in the region of the vlNTS promote the transition from inspiration to expiration and function as part of the 'Inspiratory Off Switch'.
Wasserman
A M
AM
Department of Pharmacology Georgetown University Medical Center, Washington, DC 20007, USA.
Sahibzada
N
N
Hernandez
Y M
YM
Gillis
R A
RA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002415:Cats; D007839:Functional Laterality; D001239:Inhalation / Q000187:drug effects / Q000502:physiology*; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000008:administration & dosage / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology*
D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D007736:Kynurenic Acid