Signalling mechanisms of long term facilitation of breathing with intermittent hypoxia

Pamenter, Matthew E.; Powell, Frank L.

doi:10.12703/p5-23

Cited by 11 publications

(15 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…the magnitude of vLTF was greater than the magnitude of hyperoxic ventilatory depression) indicating a sustained influence from repeated peripheral chemoreflex stimulation by acute IHH for the expression of vLTF. Moreover, this indirectly suggests a contribution from central nervous pathways, which are well established in rodent models (Pamenter & Powell, 2013), to the expression of vLTF in humans. The greater hyperoxic ventilatory depression following IHH may reflect sensory LTF of peripheral chemoreceptor afferent activity which develops over a similar time course in animal preparations (Prabhakar et al 2007).…”

Section: Main Findingsmentioning

confidence: 75%

Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

Vermeulen

Benbaruj

Brown

et al. 2020

The Journal of Physiology

View full text Add to dashboard Cite

Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that develops following intermittent hypoxia in both healthy and clinical populations. r A sustained hypercapnic background is argued to be required for full vLTF expression in humans. r We determined whether acute intermittent hypercapnic hypoxia elicits vLTF during isocapnic-normoxic recovery in healthy males and females. We further assessed whether tonic peripheral chemoreflex drive is necessary and contributes to the expression of vLTF. r Following 40 min of intermittent hypercapnic hypoxia, minute ventilation was increased throughout 50 min of isocapnic-normoxic recovery. Inhibition of peripheral chemoreflex drive with hyperoxia attenuated the magnitude of vLTF. r Males and females achieve vLTF through different respiratory recruitment patterns.

show abstract

Section: Main Findingsmentioning

confidence: 75%

Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

Vermeulen

Benbaruj

Brown

et al. 2020

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…Intermittent hypoxia causes LTF of respiratory motor nerve activity, which manifests as a persistent increase over the normoxic baseline for an hour or more after the acute HVR (298, 303). In general, ventilatory LTF primarily involves increases in V T and lasts for up to 90 min after the cessation of the final hypoxic stimulus episode.…”

Section: Physiological and Molecular Responses To Episodic Hypoxic Exmentioning

confidence: 99%

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Pamenter

Powell

2016

Comprehensive Physiology

104

101

View full text Add to dashboard Cite

Ventilatory responses to hypoxia vary widely depending on the pattern and length of hypoxic exposure. Acute, prolonged, or intermittent hypoxic episodes can increase or decrease breathing for seconds to years, both during the hypoxic stimulus, and also after its removal. These myriad effects are the result of a complicated web of molecular interactions that underlie plasticity in the respiratory control reflex circuits and ultimately control the physiology of breathing in hypoxia. Since the time domains of the physiological hypoxic ventilatory response (HVR) were identified, considerable research effort has gone toward elucidating the underlying molecular mechanisms that mediate these varied responses. This research has begun to describe complicated and plastic interactions in the relay circuits between the peripheral chemoreceptors and the ventilatory control circuits within the central nervous system. Intriguingly, many of these molecular pathways seem to share key components between the different time domains, suggesting that varied physiological HVRs are the result of specific modifications to overlapping pathways. This review highlights what has been discovered regarding the cell and molecular level control of the time domains of the HVR, and highlights key areas where further research is required. Understanding the molecular control of ventilation in hypoxia has important implications for basic physiology and is emerging as an important component of several clinical fields.

show abstract

“…These findings have led to a widespread belief that phrenic nerve and ventilatory LTF are induced by stimulation of raphe neurons and the release of serotonin onto phrenic motoneurons. This idea has received compelling support from studies that revealed that the binding of 5hydroxytryptamine (5-HT-serotonin) to 5-HT 2 receptors on phrenic motoneurons activates a cascade of cellular events, termed the Q pathway (4,10,36,40,52). This cellular pathway is emerging as a mechanistic foundation for the increase in synaptic strength between medullary bulbospinal neurons and phrenic motoneurons.…”

mentioning

confidence: 99%

“…This possibility is supported further by findings that showed that the pharmacological activation of α 1 receptors induced phrenic (9) and hypoglossal (35) motoneuron facilitation. Thus acute exposure to moderate intensities of intermittent hypoxia could result in the release and binding of norepinephrine to α 1 adrenergic receptors, which in turn, activates the same cellular pathway (i.e., the Q pathway), triggered by binding of serotonin to 5-HT 2 receptors (10,40). Additional evidence also suggests that a separate cellular pathway, referred to as the S pathway, activated via the binding of adenosine to receptors on phrenic motoneurons, may impair phrenic nerve LTF (21,36) following exposure to moderate-intermittent hypoxia.…”

mentioning

confidence: 99%

Ventilatory long-term facilitation is evident after initial and repeated exposure to intermittent hypoxia in mice genetically depleted of brain serotonin

Hickner

Hussain

Angoa‐Pérez

et al. 2014

Journal of Applied Physiology

View full text Add to dashboard Cite

Our study was designed to determine if central nervous system (CNS) serotonin is required for the induction of ventilatory long-term facilitation (LTF) in intact, spontaneously breathing mice. Nineteen tryptophan hydroxylase 2-deficient (Tph2(-/-)) mice, devoid of serotonin in the CNS, and their wild-type counterparts (Tph2(+/+)) were exposed to intermittent hypoxia each day for 10 consecutive days. The ventilatory response to intermittent hypoxia was greater in the Tph2(+/+) compared with the Tph2(-/-) mice (1.10 ± 0.10 vs. 0.77 ± 0.01 ml min(-1)·percent(-1) oxygen; P ≤ 0.04). Ventilatory LTF, caused by increases in breathing frequency, was evident in Tph2(+/+) and Tph2(-/-) mice following exposure to intermittent hypoxia each day; however, the magnitude of the response was greater in the Tph2(+/+) compared with the Tph2(-/-) mice (1.11 ± 0.02 vs. 1.05 ± 0.01 normalized to baseline on each day; P ≤ 0.01). The magnitude of ventilatory LTF increased significantly from the initial to the finals days of the protocol in the Tph2(-/-) (1.06 ± 0.02 vs. 1.11 ± 0.03 normalized to baseline on the initial days; P ≤ 0.004) but not in the Tph2(+/+) mice. This enhanced response was mediated by increases in tidal volume. Body temperature and metabolic rate did not account for differences in the magnitude of ventilatory LTF observed between groups after acute and repeated daily exposure to intermittent hypoxia. We conclude that ventilatory LTF, after acute exposure to intermittent hypoxia, is mediated by increases in breathing frequency and occurs in the absence of serotonin, although the magnitude of the response is diminished. This weakened response is enhanced following repeated daily exposure to intermittent hypoxia, via increases in tidal volume, to a similar magnitude evident in Tph2(+/+) mice. Thus the magnitude of ventilatory LTF following repeated daily exposure to intermittent hypoxia is not dependent on the presence of CNS serotonin.

show abstract

Signalling mechanisms of long term facilitation of breathing with intermittent hypoxia

Cited by 11 publications

References 73 publications

Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis

Ventilatory long-term facilitation is evident after initial and repeated exposure to intermittent hypoxia in mice genetically depleted of brain serotonin

Contact Info

Product

Resources

About