A search for genes that may confer divergent morphology and function in the carotid body between two strains of mice

Balbir, Alexander; Lee, Hannah; Okumura, Mariko; Biswal, Shyam; Fitzgerald, Robert S.; Shirahata, Machiko

doi:10.1152/ajplung.00383.2006

Cited by 37 publications

(39 citation statements)

References 115 publications

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“…The presence of leptin receptors in the rat and human carotid body have been shown by Porzionato et al (2011). In agreement with their work, our data showed high level of leptin receptor gene expression in the mouse carotid body (Balbir et al 2007). Physiological roles of leptin and its receptors in carotid body function are not known.…”

Section: 3 Resultssupporting

confidence: 92%

“…The current study, together with our previous data showing high expression of leptin receptors in the mouse carotid body (Balbir et al 2007), suggests that leptin activates leptin receptors in the carotid body and/or nerve endings and enhances CSN response to hypoxia. The results agree with our previous work, showing that leptin deficiency mice have blunted hypoxic ventilatory response (Tankersley et al 2013).…”

Section: 4 Discussionsupporting

confidence: 81%

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Is the Carotid Body a Metabolic Monitor?

Shirahata

Tang

Shin

et al. 2015

Advances in Experimental Medicine and Biology

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The carotid body is a multi-modal sensor and it has been debated if it senses low glucose. We have hypothesized that the carotid body is modified by some metabolic factors other than glucose and contributes to whole body glucose metabolism. This study examined the roles of insulin, leptin and transient receptor potential (TRP) channels on carotid sinus nerve (CSN) chemoreceptor discharge. In agreement with other studies, CSN activity was not modified by low glucose. Insulin did not affect the CSN hypoxic response. Leptin significantly augmented the CSN response to hypoxia and nonspecific Trp channel blockers (SKF96365, 2-APB) reversed the effect of leptin. Gene expression analysis showed high expression of Trpm3, 6, and 7 channels in the carotid body and petrosal ganglion. The results suggest that the adult mouse carotid body does not sense glucose levels directly. The carotid body may contribute to neural control of glucose metabolism via leptin receptor-mediated TRP channel activation.

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Section: 3 Resultssupporting

confidence: 92%

Section: 4 Discussionsupporting

confidence: 81%

Is the Carotid Body a Metabolic Monitor?

Shirahata

Tang

Shin

et al. 2015

Advances in Experimental Medicine and Biology

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“…Intercross studies of C3H/HeJ (C3) and C57BL/6J (B6) mice have mapped potential loci for the hypoxic effect and its modulation by hypercapnia [26]; however, these regions are not syntenic to human HLA gene regions. Glomus cell quantity differ across mice strains [27], and expression studies between high-and low-responder strains in carotid bodies suggest a number of potential candidates [28][29][30], but none reported have direct connections to immune function. With chronic hypoxic exposure, there is activation of the hypoxic inducible factor pathway in the carotid body [31], and hypoxia-inducible factor (HIF) is upstream to many cellular pathways, including some that affect cell-mediated immunity.…”

Section: Discussionmentioning

confidence: 99%

Ventilatory chemoresponsiveness, narcolepsy–cataplexy and human leukocyte antigen DQB1*0602 status

Han¹,

Mignot²,

Wei³

et al. 2010

Eur Respir J

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We hypothesised that hypocretin (orexin) plays a role in the determination of ventilatory chemosensitivity. 130 patients with narcolepsy-cataplexy (mean¡SD age 20¡10 yrs, 69% male) and 117 controls (22¡6.9 yrs, 62% male) were recruited and tested for human leukocyte antigen (HLA)-DQB1*0602 status, hyperoxia hypercapnic (change in minute ventilation (DV9E)/carbon dioxide tension (DPCO 2 ) L?min KEYWORDS: Chemoresponsiveness, human leukocyte antigen DQB1, hypercapnia, hypoxia, narcolepsy H ypoxic and hypercapnic sensing are processed through neuromuscular circuits resulting in an increase or decrease of tidal volume, respiratory frequency and minute ventilation (V9E). Such chemosensory reflexes operate to influence sleep apnoea, chronic obstructive pulmonary disease (COPD), heart failure, and acute adaptation to high altitude [1]. A variation in chemosensitivity across various inbred rodent strains and familial clustering of ventilatory traits in humans provides a strong rationale for gene and protein isolation efforts to unravel molecular mechanisms for these traits operating in health and disease [2].Hypocretin (orexin) is a hypothalamic neurotransmitter, which, when given intracerebroventricularly in mice, promotes both wakefulness and ventilation [3,4]. Both hypocretin knockout and hypocretin neuron-ablated mice show attenuation of respiratory excitation during fightor-flight responses [5]. Particular to chemoresponsiveness, hypocretin/orexin knockout mice have attenuated hypercapnic ventilatory responses [6]; supplementation of hypocretin-1 or -2 partially restores an attenuated response to hypercapnia, while administration of hypocretin receptor-1 antagonist will reduce hypercapnic responsiveness in wild type mice [7]. Post-hypoxic long-term facilitation, a physiological feature that is presumed to reduce sleep apnoea, is absent in hypocretin/orexin knockout mice [8].The human model of hypocretin deficiency is narcolepsy with cataplexy [9,10]. This disorder is also associated with the gene marker, human leukocyte antigen (HLA)-DQB1*0602 [11]. This disease is also considered to be associated with a higher expression of sleep-disordered breathing [12,13]. Our primary hypothesis was that an impaired chemoresponsiveness would be present

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“…In addition, carotid bodies from PM-challenged CREB A133 mice exhibited marked gene up-regulation of Na 1 channels (scnn1b and scn8a) and Na 1 -Ca 1 exchangers (slc8a1) with concomitant down-regulation of K 1 channels (kcnd3, kcnmb2, kcnc1, kcnd1, and kcnd2), responses which potentially contribute to hyperexcitability of carotid body sensory activity (16,38). Furthermore, significant down-regulation of glial-derived neurotrophic factor (GDNF), which is critical for maintenance of the dopaminergic phenotype of hypoxic-sensing type I carotid body cells (39), was observed in PM-challenged CREB A133 mice (Table E1).…”

Section: Genomic Analyses To Evaluate Gene Deregulation In Chf Micementioning

confidence: 99%

Particulate Matter Induces Cardiac Arrhythmias via Dysregulation of Carotid Body Sensitivity and Cardiac Sodium Channels

Wang¹,

Lang²,

Moreno‐Vinasco³

et al. 2012

Am J Respir Cell Mol Biol

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The mechanistic links between exposure to airborne particulate matter (PM) pollution and the associated increases in cardiovascular morbidity and mortality, particularly in people with congestive heart failure (CHF), have not been identified. To advance understanding of this issue, genetically engineered mice (CREB A133 ) exhibiting severe dilated cardiomyopathic changes were exposed to ambient PM collected in Baltimore. CREB A133 mice, which display aberrant cardiac physiology and anatomy reminiscent of human CHF, displayed evidence of basal autonomic aberrancies (compared with wild-type mice) with PM exposure via aspiration, producing significantly reduced heart rate variability, respiratory dysynchrony, and increased ventricular arrhythmias. Carotid body afferent nerve responses to hypoxia and hyperoxia-induced respiratory depression were pronounced in PM-challenged CREB A133 mice, and denervation of the carotid bodies significantly reduced PM-mediated cardiac arrhythmias. Genome-wide expression analyses of CREB A133 left ventricular tissues demonstrated prominent Na 1 and K 1 channel pathway gene dysregulation. Subsequent PM challenge increased tyrosine phosphorylation and nitration of the voltage-gated type V cardiac muscle a-subunit of the Na 1 channel encoded by SCN5A. Ranolazine, a Na 1 channel modulator that reduces late cardiac Na 1 channel currents, attenuated PM-mediated cardiac arrhythmias and shortened PMelongated QT intervals in vivo. These observations provide mechanistic insights into the epidemiologic findings in susceptibility of human CHF populations to PM exposure. Our results suggest a multiorgan pathobiology inherent to the CHF phenotype that is exaggerated by PM exposure via heightened carotid body sensitivity and cardiac Na 1 channel dysfunction.

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A search for genes that may confer divergent morphology and function in the carotid body between two strains of mice

Cited by 37 publications

References 115 publications

Is the Carotid Body a Metabolic Monitor?

Is the Carotid Body a Metabolic Monitor?

Ventilatory chemoresponsiveness, narcolepsy–cataplexy and human leukocyte antigen DQB1*0602 status

Particulate Matter Induces Cardiac Arrhythmias via Dysregulation of Carotid Body Sensitivity and Cardiac Sodium Channels

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