Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla

Moreira, Thiago dos Santos; Wenker, Ian C.; Sobrinho, Cleyton R.; Barna, Bárbara; Takakura, Ana C.; Mulkey, Daniel K.

doi:10.1113/jphysiol.2014.284430

Cited by 15 publications

(23 citation statements)

References 66 publications

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“…Although transduction mechanisms remain undefined, a number of potential mechanisms may be excluded from con-sideration as contributors to the current results. For example, although pH/CO 2 sensitivity in the regions such as the retrotrapezoid nucleus is contributed to by astrocytes (Moreira et al 2015), glia are believed to play no role in raphe 5-HT neuron chemosensory transduction (Sobrinho et al 2014;Wu et al 2013). Similarly, despite the implication of acid-sensitive TASK channels in this process (Bayliss et al 2015;Putnam et al 2004), chemosensitivity of raphe 5-HT neurons does not appear to be dependent on TASK channels (Massey et al 2015;Wu et al 2008).…”

Section: Lmx1bmentioning

confidence: 99%

Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Corcoran

Richerson

Harris

2015

Journal of Neurophysiology

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Corcoran AE, Richerson GB, Harris MB. Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity. J Neurophysiol 114: 381-389, 2015. First published April 15, 2015 doi:10.1152/jn.00870.2013.-Serotonin (5-HT)-synthesizing neurons of the medullary raphe are putative central chemoreceptors, proposed to be one of potentially multiple brain stem chemosensitive cell types and loci interacting to produce the respiratory chemoreflex. Hypocretin-synthesizing neurons of the lateral hypothalamus are important contributors to arousal state, thermoregulation, and feeding behavior and are also reportedly involved in the hypercapnic ventilatory response. Recently, a functional interaction was found between the hypocretin system and 5-HT neurons of the dorsal raphe. The validity and potential significance of hypocretin modulation of medullary raphe 5-HT neurons, however, is unknown. As such, the purpose of this study was to explore functional interactions between the hypocretin system and 5-HT system of the medullary raphe on baseline respiratory output and central chemosensitivity.To explore such interactions, we used the neonatal in vitro medullary slice preparation derived from wild-type (WT) mice (normal 5-HT function) and a knockout strain lacking all central 5-HT neurons (Lmx1b f/f/p mice). We examined effects of acidosis, hypocretin-1, a hypocretin receptor antagonist (SB-408124), and the effect of the antagonist on the response to acidosis. We confirmed the critical role of 5-HT neurons in central chemosensitivity given that the increased hypoglossal burst frequency with acidosis, characteristic of WT mice, was absent in preparations derived from Lmx1b f/f/p mice. We also found that hypocretin facilitated baseline neural ventilatory output in part through 5-HT neurons. Although the impact of hypocretin on 5-HT neuronal sensitivity to acidosis is still unclear, hypocretins did appear to mediate the burst duration response to acidosis via serotonergic mechanisms.hypocretin; serotonin; ventilation; chemosensitivity THE BRAIN'S RESPONSIVENESS to pH/CO 2 (central chemosensitivity) has been proposed to be a distributed network function involving multiple chemoreceptive sites in the brain stem (Nattie and Li 2009). Growing evidence identifies a distinct subset of 5-HT neurons of the medullary raphe as critical for chemosensitivity (Brust et al. 2014;Corcoran et al. 2009Corcoran et al. , 2013Richerson 2004). Much effort has been directed at understanding how multiple chemoreceptive cells and loci interact and modulate each other and/or the respiratory rhythm itself (Dias et al. 2008(Dias et al. , 2009Iceman et al. 2014;Li et al. 2006;Mulkey et al. 2007).Recently, neurons containing hypocretin neuropeptides (hypocretin-1/orexin A and hypocretin-2/orexin B) were proposed to influence CO 2 sensitivity (Dias et al. 2009;Nakamura et al. 2007). The hypocretin system is anatomically linked with central chemosensory and respiratory nuclei (Fung et al. 2001;Hagan et al. ...

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Section: Lmx1bmentioning

confidence: 99%

Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Corcoran

Richerson

Harris

2015

Journal of Neurophysiology

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“…; Moreira et al . ). Interestingly, Marina and collegues () showed that ATP release from astrocytes activates pre‐sympathetic brainstem neurones in the RVLM, thereby contributing to symphatoexcitacion, progression of ventricular remodelling and development of heart failure secondary to myocardial infarction (Marina et al .…”

Section: Introductionmentioning

confidence: 97%

Contribution of peripheral and central chemoreceptors to sympatho‐excitation in heart failure

Toledo

Andrade

Lucero

et al. 2016

The Journal of Physiology

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Chronic heart failure (CHF) is a major public health problem. Tonic hyper-activation of sympathetic neural outflow is commonly observed in patients with CHF. Importantly, sympatho-excitation in CHF exacerbates its progression and is strongly related to poor prognosis and high mortality risk. Increases in both peripheral and central chemoreflex drive are considered markers of the severity of CHF. The principal peripheral chemoreceptors are the carotid bodies (CBs) and alteration in their function has been described in CHF. Mainly, during CHF the CB chemosensitivity is enhanced leading to increases in ventilation and sympathetic outflow. In addition to peripheral control of breathing, central chemoreceptors (CCs) are considered a dominant mechanism in ventilatory regulation. Potentiation of the ventilatory and sympathetic drive in response to CC activation has been shown in patients with CHF as well as in animal models. Therefore, improving understanding of the contribution of the peripheral and central chemoreflexes to augmented sympathetic discharge in CHF could help in developing new therapeutic approaches intended to attenuate the progression of CHF. Accordingly, the main focus of this review is to discuss recent evidence that peripheral and central chemoreflex function are altered in CHF and that they contribute to autonomic imbalance and progression of CHF. Abstract figure legend Chronic heart failure is characterized by exacerbation of the peripheral and central chemoreflexes, which contributes to the establishment and progression of sympathoexcitation and breathing disorders. Importantly, chemoreflex activation is strongly associated with cardiac arrhythmogenesis, cardiac adverse remodelling, periodic breathing and central apnoeas and hypopnoeas.

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“…The review by Moreira and colleagues entitled ‘Independent purinergic mecha‐nisms of central and peripheral chemoreception in the rostral ventrolateral medulla.’ describes the role of purinergic signalling at the level of the ventrolateral medulla in coordinating cardiorespiratory responses to hypoxia and hypercapnia by activating RTN chemoreceptors and presympathetic C1 neurons (Moreira et al . ). In the context of central chemoreception, evidence suggests that RTN astrocytes respond to high CO 2 by releasing ATP via connexin 26 hemichannels (Huckstepp et al .…”

mentioning

confidence: 97%

New advances in the neural control of breathing

Moreira

Mulkey

2015

The Journal of Physiology

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Independent purinergic mechanisms of central and peripheral chemoreception in the rostral ventrolateral medulla

Cited by 15 publications

References 66 publications

Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Functional link between the hypocretin and serotonin systems in the neural control of breathing and central chemosensitivity

Contribution of peripheral and central chemoreceptors to sympatho‐excitation in heart failure

New advances in the neural control of breathing

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