a(CHEBI:choline)
Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1) PubMed:26813123
Although cholinergic neurons can synthesize choline, the de novo synthesis contributes only with a very small fraction of the total choline that is needed for ACh synthesis (see Fig. 1) PubMed:26813123
CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh PubMed:26813123
Interestingly, it has been demonstrated that an increase in neuronal firing can lead to an increase in choline uptake and in the synthesis of ACh PubMed:26813123
It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123
Choline that is released by ACh hydrolysis in the synaptic cleft is continuously reuptaken into the presynaptic cholinergic neuron by an active transport system (see Fig. 1) PubMed:26813123
Two choline transporters have been identified in neurons: a ubiquitous, low-affinity, sodium-independent transporter that can only be inhibited by high concentrations of hemicholinium-3 (HC-3) (Ki of about 50 μM), and a highaffinity, sodium-dependent, HC-3-sensitive (Ki of 10-100 nM) choline transporter (CHT1) PubMed:26813123
It is possible that the presence of CHT1 in the membrane of synaptic vesicles and the consequent increase in CHT1 relocation to the plasma membrane following neuronal depolarization could explain why an increase in neuronal firing promotes increased choline reuptake and, thus, ACh synthesis PubMed:26813123
In addition, quantitative autoradiography assay revealed that choline uptake was reduced in the hippocampus of these animals and that the expression of muscarinic and nicotinic cholinergic receptors was diminished PubMed:26813123
As shown in Fig. 5, A–C, nifedipine was found to decrease the peak calcium response to choline in PC12 cells (peak: 795.00% ΔF/Fθ ± 107.1%) by 56.94% (p = 0.003), whereas prolonging the duration of the choline-induced calcium transient (AUC: 749.50% ΔF/Fθ2 × s ± 64.02%) in the same cell. PubMed:26088141
In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141
Treatment of PC12 cells with 10 mM choline was associated with a translocation of PH-mCherry from the cell surface as determined by the presence of the fluorescence signal within 1 μm of the edge of the cell into the cytosol of the GC (Fig. 6, A and B). Pre-treatment of cells with SP abolished this translocation (Fig. 6B). PubMed:26088141
PC12 cells transfected with α7345–348A showed a reduction in choline-mediated calcium responses. PubMed:26088141
Variants in the gene for phosphatidylethanolamine methyl transferase, which synthesizes phosphatidylcholine and thus provides a source of choline, are also associated with choline deficiency and with schizophrenia PubMed:21482353
using in vivo proton NMR imaging, levels of choline (the rate-limiting precursor to endogeneous ACh) were shown to be increased in the brains of patients with depression217 and in the prefrontal cortex of adolescents with depression218 compared with the control group. PubMed:19721446
Another important aspect of this diffusive ACh signal is that its eventual hydrolysis creates choline, which also activates and desensitizes nAChRs in a subtype-selective manner (54, 55). PubMed:17009926
CHT1 is mainly found in cholinergic neurons [92-94] and is responsible for supplying choline for the synthesis of ACh PubMed:26813123
PC12 cells transfected with α7345–348A showed a reduction in choline-mediated calcium responses. PubMed:26088141
In α7345–348A nAChR expressing cells, nifedipine had no effect on the peak or the duration of the calcium transient (peak: 957.00% ΔF/Fθ ± 252.2%; AUC: 333.33% ΔF/Fθ2 × s ± 91.53%) relative to choline treatment alone (Fig. 5, A–C). The findings suggest that choline-induced calcium responses in PC12 cells involve the activity of VGCC (37, 38). PubMed:26088141
Treatment of PC12 cells with 10 mM choline was associated with a translocation of PH-mCherry from the cell surface as determined by the presence of the fluorescence signal within 1 μm of the edge of the cell into the cytosol of the GC (Fig. 6, A and B). Pre-treatment of cells with SP abolished this translocation (Fig. 6B). PubMed:26088141
Sequential imaging of PH-mCherry and GCaMP5G confirms that choline promotes a rise in intracellular calcium and PH-mCherry translocation in the same cellular compartment (Fig. 6, B and C). Cytoplasmic translocation of PH-mCherry occurred on a slower time scale (40 s after choline application) than peak calcium responses (∼1 s after choline application). These kinetics are consistent with the translocation of the PH domain sensor in the cell (20, 29). PubMed:26088141
As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141
As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141
As shown in Fig. 8, A and B, IP of the α7 using the C-20 antibody suggests that choline application attenuates G protein binding with the nAChR. Choline treatment resulted in a 56% reduction in Gαq and 47% reduction in Gβ association within the α7 nAChR complex (Fig. 8B). PubMed:26088141
As we will see below, the mystery of somatodendritic nAChRs can also be resolved by the sensitivity of alpha7 nAChRs to constant levels of another agonist, choline PubMed:21482353
A possible candidate is choline, which, in addition to its other development roles, activates alpha7 nAChRs at levels several fold higher than acetylcholine PubMed:21482353
Choline, like nicotine, can protect neural cells from cytotoxicity that is induced by growth factor deprivation152 or exposure to the glutamate analogue AMPA (alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid)153. PubMed:19721446
Choline, like nicotine, can protect neural cells from cytotoxicity that is induced by growth factor deprivation152 or exposure to the glutamate analogue AMPA (alpha-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid)153. PubMed:19721446
BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.
If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.