A GABAergic inhibitory microcircuit controlling cholinergic outflow to the airways

2004 ◽  
Vol 96 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Constance T. Moore ◽  
Christopher G. Wilson ◽  
Catherine A. Mayer ◽  
Sandra S. Acquah ◽  
V. John Massari ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Structural Characteristics ◽  
Nucleus Ambiguus ◽  
Acid Decarboxylase ◽  
Electron Microscopic ◽  
Synaptic Contacts ◽  
Smooth Muscle Tone ◽  
Rostral Nucleus

GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses ( P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger ( P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.

Activation of the midbrain periaqueductal gray induces airway smooth muscle relaxation

2002 ◽  
Vol 93 (2) ◽  
pp. 440-449 ◽  
Author(s):  
Musa A. Haxhiu ◽  
Bryan K. Yamamoto ◽  
Ismail A. Dreshaj ◽  
Donald G. Ferguson
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Muscle Relaxation ◽  
Gaba Release ◽  
Periaqueductal Gray ◽  
Nucleus Ambiguus ◽  
Smooth Muscle Relaxation ◽  
Receptor Subtype ◽  
Smooth Muscle Tone

In this study, we examined effects of chemical stimulation of the ventrolateral region of the midbrain periaqueductal gray (vl PAG) on airway smooth muscle tone. We observed that in anesthetized, paralyzed, and artificially ventilated ferrets, vl PAG stimulation elicited airway smooth muscle relaxation. To clarify the mechanisms underlying this observation, we examined the GABA-GABAA receptor signaling pathway by 1) examining the expression of GABAA receptors on airway-related vagal preganglionic neurons (AVPNs) located in the rostral nucleus ambiguus region (rNA), by use of receptor immunochemistry and confocal microscopy; 2) measuring GABA release within the rNA by using microdialysis; and 3) performing physiological experiments to determine the effects of selective blockade of GABAA receptors expressed by AVPNs in the rNA region on vl PAG-induced airway relaxation, thereby defining the role of the GABAA receptor subtype in this process. We observed that AVPNs located in the rNA region do express the GABAA receptor β-subtype. In addition, we demonstrated that activation of vl PAG induced GABA release within the rNA region, and this release was associated with airway smooth muscle relaxation. Blockade of the GABAA receptor subtype expressed by AVPNs in the rNA by bicuculline diminished the inhibitory effects of vl PAG stimulation on airway smooth muscle tone. These data indicate, for the first time, that activation of vl PAG dilates the airways by a release of GABA and activation of GABAA receptors expressed by AVPNs.

Airway basement membrane perimeter in human airways is not a constant; potential implications for airway remodeling in asthma

2004 ◽  
Vol 97 (2) ◽  
pp. 556-563 ◽  
Author(s):  
Brent E. McParland ◽  
Peter D. Paré ◽  
Peter R. A. Johnson ◽  
Carol L. Armour ◽  
Judith L. Black
Keyword(s):  
Smooth Muscle ◽  
Basement Membrane ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Airway Remodeling ◽  
Organ Bath ◽  
Smooth Muscle Tone ◽  
Asthmatic Patients ◽  
Constant Potential ◽  
Human Airways

Many studies that demonstrate an increase in airway smooth muscle in asthmatic patients rely on the assumption that bronchial internal perimeter ( Pi) or basement membrane perimeter ( Pbm) is a constant, i.e., not affected by fixation pressure or the degree of smooth muscle shortening. Because it is the basement membrane that has been purported to be the indistensible structure, this study examines the assumption that Pbm is not affected by fixation pressure. Pbm was determined for the same human airway segment ( n = 12) fixed at distending pressures of 0 cmH2O and 21 cmH2O in the absence of smooth muscle tone. Pbm for the segment fixed at 0 cmH2O was determined morphometrically, and the Pbm for the same segment, had the segment been fixed at 21 cmH2O, was predicted from knowing the luminal volume and length of the airway when distended to 21 cmH2O (organ bath-derived Pi). To ensure an accurate transformation of the organ bath-derived Pi value to a morphometry-derived Pbm value, had the segment been fixed at 21 cmH2O, the relationship between organ bath-derived Pi and morphometry-derived Pbm was determined for five different bronchial segments distended to 21 cmH2O and fixed at 21 cmH2O ( r2 = 0.99, P < 0.0001). Mean Pbm for bronchial segments fixed at 0 cmH2O was 9.4 ± 0.4 mm, whereas mean predicted Pbm, had the segments been fixed at 21 cmH2O, was 14.1 ± 0.5 mm ( P < 0.0001). This indicates that Pbm is not a constant when isolated airway segments without smooth muscle tone are fixed distended to 21 cmH2O. The implication of these results is that the increase in smooth muscle mass in asthma may have been overestimated in some previous studies. Therefore, further studies are required to examine the potential artifact using whole lungs with and without abolition of airway smooth muscle tone and/or inflation.

Direct effects of hydrogen peroxide on airway smooth muscle tone: Roles of Ca2+ influx and Rho-kinase

2007 ◽  
Vol 556 (1-3) ◽  
pp. 151-156 ◽  
Author(s):  
Katsuyuki Kojima ◽  
Hiroaki Kume ◽  
Satoru Ito ◽  
Tetsuya Oguma ◽  
Akira Shiraki ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Rho Kinase ◽  
Direct Effects ◽  
Smooth Muscle Tone

scholarly journals The role of Eserine and GABA in the activity of DMV on airway smooth muscle tone in ferrets

2007 ◽  
Vol 21 (6) ◽  
Author(s):  
Burim Neziri ◽  
Shaip Krasniqi ◽  
Muharrem Jakupaj ◽  
Shqipe Devaja
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Tone

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

2004 ◽  
Vol 97 (4) ◽  
pp. 1508-1517 ◽  
Author(s):  
Prabha Kc ◽  
Catherine A. Mayer ◽  
Musa A. Haxhiu
Keyword(s):  
Smooth Muscle ◽  
Muscarinic Receptor ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Relaxation ◽  
Receptor Blockade ◽  
Double Labeling ◽  
Smooth Muscle Tone ◽  
Preganglionic Neurons ◽  
Stimulation Of

In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin β-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.

Chest wall distortion and discharge of pulmonary slowly adapting receptors

1992 ◽  
Vol 73 (4) ◽  
pp. 1619-1625 ◽  
Author(s):  
S. Iscoe ◽  
S. P. Gordon
Keyword(s):  
Smooth Muscle ◽  
Chest Wall ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Respiratory Neurons ◽  
Lung Inflation ◽  
Smooth Muscle Tone ◽  
Residual Capacity ◽  
Discharge Patterns ◽  
Spontaneously Breathing

We assessed the effects of chest wall distortion, changes in lung volume, and abolition of airway smooth muscle tone on the discharge patterns of 92 pulmonary slowly adapting receptors (SAR) in decerebrate, spontaneously breathing cats. Distortion resulted from their inspiratory efforts against an occluded airway at functional residual capacity and at increased end-expiratory lung volumes. Approximately 40% of SAR increased discharge frequencies during occlusions. Modulation of SAR discharge during occlusions persisted after administration of atropine to eliminate airway smooth muscle tone. Phasic modulation of SAR discharge was eliminated during no-inflation tests after paralyzing the cats and ventilating them on a cycle-triggered pump. We conclude 1) parasympathetic modulation of airway smooth muscle tone makes no obvious contribution to SAR discharge in spontaneously breathing cats; 2) the no-inflation test (withholding of lung inflation during neural inspiration) in paralyzed and ventilated cats is a valid test for the presence of projections from SAR to medullary respiratory neurons; and 3) in the absence of tidal volume changes, distortion stimulates some SAR. Sensory feedback from receptors in the lung, not just those in the chest wall, may therefore provide information about abnormal chest wall configurations.

Prostaglandin Regulation of Airway Smooth Muscle Tone

1973 ◽  
Vol 245 (142) ◽  
pp. 84-85 ◽  
Author(s):  
J. OREHEK ◽  
J. S. DOUGLAS ◽  
A. J. LEWIS ◽  
A. BOUHUYS
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Tone ◽  
Smooth Muscle Tone
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