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Functional glutamate transporters are expressed in the carotid chemoreceptor.

ABSTRACT: BACKGROUND:The carotid body (CB) plays a critical role in cyclic intermittent hypoxia (CIH)-induced chemosensitivity; however, the underlying mechanism remains uncertain. We have demonstrated the presence of multiple inotropic glutamate receptors (iGluRs) in CB, and that CIH exposure alters the level of some iGluRs in CB. This result implicates glutamatergic signaling in the CB response to hypoxia. The glutamatergic neurotransmission is not only dependent on glutamate and glutamate receptors, but is also dependent on glutamate transporters, including vesicular glutamate transporters (VGluTs) and excitatory amino acid transporters (EAATs). Here, we have further assessed the expression and distribution of VGluTs and EAATs in human and rat CB and the effect of CIH exposure on glutamate transporters expression. METHODS:The mRNA of VGluTs and EAATs in the human CB were detected by RT-PCR. The protein expression of VGluTs and EAATs in the human and rat CB were detected by Western blot. The distribution of VGluT3, EAAT2 and EAAT3 were observed by immunohistochemistry staining and immunofluorescence staining. Male Sprague-Dawley (SD) rats were exposed to CIH (FIO2 10-21%, 3?min/3?min for 8?h per day) for 2?weeks. The unpaired Student's t-test was performed. RESULTS:Here, we report on the presence of mRNAs for VGluT1-3 and EAAT1-3 in human CB, which is consistent with our previous results in rat CB. The proteins of VGluT1 and 3, EAAT2 and 3, but not VGluT2 and EAAT1, were detected with diverse levels in human and rat CB. Immunostaining showed that VGluT3, the major type of VGluTs in CB, was co-localized with tyrosine hydroxylase (TH) in type I cells. EAAT2 and EAAT3 were distributed not only in type I cells, but also in glial fibrillary acidic protein (GFAP) positive type II cells. Moreover, we found that exposure of SD rats to CIH enhanced the protein level of EAAT3 as well as TH, but attenuated the levels of VGluT3 and EAAT2 in CB. CONCLUSIONS:Our study suggests that glutamate transporters are expressed in the CB, and that glutamate transporters may contribute to glutamatergic signaling-dependent carotid chemoreflex to CIH.

SUBMITTER: Li C

PROVIDER: S-EPMC7414757 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Functional glutamate transporters are expressed in the carotid chemoreceptor.

Li Chaohong C Huang Lu L Jia Xianglei X Zhao Baosheng B Chen Lingyun L Liu Yuzhen Y

Respiratory research 20200808 1

<h4>Background</h4>The carotid body (CB) plays a critical role in cyclic intermittent hypoxia (CIH)-induced chemosensitivity; however, the underlying mechanism remains uncertain. We have demonstrated the presence of multiple inotropic glutamate receptors (iGluRs) in CB, and that CIH exposure alters the level of some iGluRs in CB. This result implicates glutamatergic signaling in the CB response to hypoxia. The glutamatergic neurotransmission is not only dependent on glutamate and glutamate recep ...[more]

PMID: 32771007

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Project description:ObjectivesThis study sought to investigate whether selective ablation of the carotid body (CB) chemoreceptors improves cardiorespiratory control and survival during heart failure.BackgroundChronic heart failure (CHF) is a recognized health problem worldwide, and novel treatments are needed to better improve life quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is thought to contribute significantly to autonomic dysfunction, abnormal breathing patterns, and increased mortality in heart failure.MethodsChronic heart failure was induced by coronary ligation in rats. Selective CB denervation was performed to remove carotid chemoreflex drive in the CHF state (16 weeks post-myocardial infarction). Indexes of autonomic and respiratory function were assessed in CB intact and CB denervated animals. CB denervation at 2 weeks post-myocardial infarction was performed to evaluate whether early targeted CB ablation decreases the progression of left ventricular dysfunction, cardiac remodeling, and arrhythmic episodes and improves survival.ResultsThe CHF rats developed increased CB chemoreflex drive and chronic central pre-sympathetic neuronal activation, increased indexes of elevated sympathetic outflow, increased breathing variability and apnea incidence, and desensitization of the baroreflex. Selective CB ablation reduced the central pre-sympathetic neuronal activation by 40%, normalized indexes of sympathetic outflow and baroreflex sensitivity, and reduced the incidence of apneas in CHF animals from 16.8 ± 1.8 events/h to 8.0 ± 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac remodeling, deterioration of left ventricle ejection fraction, and cardiac arrhythmias were reduced. Most importantly, the rats that underwent early CB ablation exhibited an 85% survival rate compared with 45% survival in CHF rats without the intervention.ConclusionsCarotid chemoreceptors play a seminal role in the pathogenesis of heart failure, and their targeted ablation might be of therapeutic value to reduce cardiorespiratory dysfunction and improve survival during CHF.

Project description:BackgroundMarine molluscs, as is the case with most aquatic animals, rely heavily on olfactory cues for survival. In the mollusc Aplysia californica, mate-attraction is mediated by a blend of water-borne protein pheromones that are detected by sensory structures called rhinophores. The expression of G protein and phospholipase C signaling molecules in this organ is consistent with chemosensory detection being via a G-protein-coupled signaling mechanism.ResultsHere we show that novel multi-transmembrane proteins with similarity to rhodopsin G-protein coupled receptors are expressed in sensory epithelia microdissected from the Aplysia rhinophore. Analysis of the A. californica genome reveals that these are part of larger multigene families that possess features found in metazoan chemosensory receptor families (that is, these families chiefly consist of single exon genes that are clustered in the genome). Phylogenetic analyses show that the novel Aplysia G-protein coupled receptor-like proteins represent three distinct monophyletic subfamilies. Representatives of each subfamily are restricted to or differentially expressed in the rhinophore and oral tentacles, suggesting that they encode functional chemoreceptors and that these olfactory organs sense different chemicals. Those expressed in rhinophores may sense water-borne pheromones. Secondary signaling component proteins Galphaq, Galphai, and Galphao are also expressed in the rhinophore sensory epithelium.ConclusionThe novel rhodopsin G-protein coupled receptor-like gene subfamilies identified here do not have closely related identifiable orthologs in other metazoans, suggesting that they arose by a lineage-specific expansion as has been observed in chemosensory receptor families in other bilaterians. These candidate chemosensory receptors are expressed and often restricted to rhinophores and oral tentacles, lending support to the notion that water-borne chemical detection in Aplysia involves species- or lineage-specific families of chemosensory receptors.

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Functional glutamate transporters are expressed in the carotid chemoreceptor.

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Functional glutamate transporters are expressed in the carotid chemoreceptor.

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