論文 - 詳細
| RRC ID | 52308 |
|---|---|
| 著者 | Ishii T, Homma K, Mano A, Akagi T, Shigematsu Y, Shimoda Y, Inoue H, Kakinuma Y, Kaneda M. |
| タイトル | Novel channel-mediated choline transport in cholinergic neurons of the mouse retina. |
| ジャーナル | J Neurophysiol |
| Abstract |
Choline uptake into the presynaptic terminal of cholinergic neurons is mediated by the high-affinity choline transporter and is essential for acetylcholine synthesis. In a previous study, we reported that P2X2 purinoceptors are selectively expressed in OFF-cholinergic amacrine cells of the mouse retina. Under specific conditions, P2X2 purinoceptors acquire permeability to large cations, such as N-methyl-d-glucamine, and therefore potentially could act as a noncanonical pathway for choline entry into neurons. We tested this hypothesis in OFF-cholinergic amacrine cells of the mouse retina. ATP-induced choline currents were observed in OFF-cholinergic amacrine cells, but not in ON-cholinergic amacrine cells, in mouse retinal slice preparations. High-affinity choline transporters are expressed at higher levels in ON-cholinergic amacrine cells than in OFF-cholinergic amacrine cells. In dissociated preparations of cholinergic amacrine cells, ATP-activated cation currents arose from permeation of extracellular choline. We also examined the pharmacological properties of choline currents. Pharmacologically, α,β-methylene ATP did not produce a cation current, whereas ATPγS and benzoyl-benzoyl-ATP (BzATP) activated choline currents. However, the amplitude of the choline current activated by BzATP was very small. The choline current activated by ATP was strongly inhibited by pyridoxalphosphate-6-azophenyl-2',4'-sulfonic acid. Accordingly, P2X2 purinoceptors expressed in HEK-293T cells were permeable to choline and similarly functioned as a choline uptake pathway. Our physiological and pharmacological findings support the hypothesis that P2 purinoceptors, including P2X2 purinoceptors, function as a novel choline transport pathway and may provide a new regulatory mechanism for cholinergic signaling transmission at synapses in OFF-cholinergic amacrine cells of the mouse retina.NEW & NOTEWORTHY Choline transport across the membrane is exerted by both the high-affinity and low-affinity choline transporters. We found that choline can permeate P2 purinergic receptors, including P2X2 purinoceptors, in cholinergic neurons of the retina. Our findings show the presence of a novel choline transport pathway in cholinergic neurons. Our findings also indicate that the permeability of P2X2 purinergic receptors to choline observed in the heterologous expression system may have a physiological relevance in vivo. |
| 巻・号 | 118(4) |
| ページ | 1952-1961 |
| 公開日 | 2017-10-1 |
| DOI | 10.1152/jn.00506.2016 |
| PII | jn.00506.2016 |
| PMID | 28701543 |
| PMC | PMC5626900 |
| MeSH | Adenosine Triphosphate / metabolism Adenosine Triphosphate / pharmacology Amacrine Cells / metabolism* Amacrine Cells / physiology Animals Cells, Cultured Choline / metabolism* Cholinergic Neurons / metabolism* Cholinergic Neurons / physiology HEK293 Cells Humans Mice Mice, Inbred C57BL Purinergic P2X Receptor Agonists / pharmacology Purinergic P2X Receptor Antagonists / pharmacology Pyridoxal Phosphate / analogs & derivatives Pyridoxal Phosphate / pharmacology Receptors, Purinergic P2X2 / metabolism* Retinal Neurons / metabolism* Retinal Neurons / physiology |
| IF | 2.234 |
| 引用数 | 2 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293T(RCB2202) |