2018
DOI: 10.3389/fphys.2018.00362
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Modulation of Connexin-36 Gap Junction Channels by Intracellular pH and Magnesium Ions

Abstract: Connexin-36 (Cx36) protein forms gap junction (GJ) channels in pancreatic beta cells and is also the main Cx isoform forming electrical synapses in the adult mammalian brain. Cx36 GJs can be regulated by intracellular pH (pHi) and cytosolic magnesium ion concentration ([Mg2+]i), which can vary significantly under various physiological and pathological conditions. However, the combined effect and relationship of these two factors over Cx36-dependent coupling have not been previously studied in detail. Our exper… Show more

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Cited by 20 publications
(15 citation statements)
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“…The unique crossover design allowed us to include responses of the same participants to all three experimental variants, NBR, HBR, and HAmb, under the controlled nutritional, environmental, and experimental conditions. The same general trends of body deconditioning were recovered in this study based on 1 H-NMR metabolomics of urine, as described before using different sets of markers and approaches in the PlanHab subprojects ( Debevec et al, 2014a , 2016b ; Rittweger et al, 2016 ; Simpson et al, 2016 ; Strewe et al, 2017 , 2018 ; Stavrou et al, 2018a , b ; Supplementary Table 1 ). This shows large congruence between the various independently collected datasets within the PlanHab and the metabolomics approach used in this study.…”
Section: Discussionmentioning
confidence: 52%
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“…The unique crossover design allowed us to include responses of the same participants to all three experimental variants, NBR, HBR, and HAmb, under the controlled nutritional, environmental, and experimental conditions. The same general trends of body deconditioning were recovered in this study based on 1 H-NMR metabolomics of urine, as described before using different sets of markers and approaches in the PlanHab subprojects ( Debevec et al, 2014a , 2016b ; Rittweger et al, 2016 ; Simpson et al, 2016 ; Strewe et al, 2017 , 2018 ; Stavrou et al, 2018a , b ; Supplementary Table 1 ). This shows large congruence between the various independently collected datasets within the PlanHab and the metabolomics approach used in this study.…”
Section: Discussionmentioning
confidence: 52%
“…The approach adopted in this study provides an opportunity to generate new hypotheses on metabolic pathway perturbation. One can indeed hypothesize that the metabolites involved in metabolic pathways identified in this study in fact act as signaling molecules [or account for lack of these (e.g., in HBR, NBR)] involved in the PlanHab symptoms as detailed in Figure 1 : insulin resistance, low-grade inflammation, different mitochondrial function, miRNA expression in large muscles, differences in lipid oxidation, mood changes, and depression ( Debevec et al, 2014a , 2016b ; Rittweger et al, 2016 ; Simpson et al, 2016 ; Sket et al, 2017a , b , 2018 ; Strewe et al, 2017 , 2018 ; Stavrou et al, 2018a , b ; Supplementary Table 1 ). In addition to those listed above, groups of metabolites identified in this study were also associated with: (i) the chronic obstructive pulmonary disease (COPD) ( Adamko et al, 2015 ; Za̧bek et al, 2015 ) and included metabolites such as 3-hydroxyisovalerate, 2-hydroxyisobutyrate, creatinine, formate, taurine, urea, choline, isoleucine, pantothenate, valine, and its degradation to beta-aminoisobutyric acid during metabolism of branched-chain amino acids suggest increased catabolism associated with COPD; (ii) cardiovascular disease as a results of associated chain of events such as tissue hypoxia (gut ischemia) due to reduced oxidative phosphorylation and energy production that lead to pulmonary hypertension, systemic inflammatory responses, and increased risk of cardiovascular disease, type 2 diabetes, depression, and osteoporosis ( Jones, 2014 ).…”
Section: Discussionmentioning
confidence: 89%
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“…These channels, through which cells are electrically and chemically coupled, can be formed from homomeric or heteromeric hemichannels, and are therefore called homotypic or heterotypic channels, respectively. The conductance of these Cxs-based channels and hemichannels is regulated by calcium concentration [13,14], intracellular pH [15,16,17,18], some neurotransmitters, such as serotonin and dopamine [19,20], the trans-junctional voltage (relative voltage difference between coupled cells), and the membrane voltage [21,22]. The conductance is related to the type of Cxs that make up the channels and hemichannels; for example, Cx36 has a conductance of 10–15 pS, while Cx45 and Cx43 have a conductance of 27.84 ± 0.25 pS [23,24,25] and 36.8 ± 0.54 pS [25], respectively.…”
Section: Molecular and Cellular Characteristics Of Connexins-basedmentioning
confidence: 99%
“…The regulation of gap junction function is significant for cell communication. Cytoplasmic pH, Ca 2+ , voltage, oncogenes, nucleotides, hormones, neurotransmitters, lipids, growth factors, and many exogenous chemicals can regulate function of gap junction by different levels including transcription, translation and post-translation modification, which is achieved by a variety of mechanisms [11][12][13][14].…”
Section: Function Of Gjmentioning
confidence: 99%