Regulation of synaptic acetylcholine concentrations by acetylcholine transport in rat striatal cholinergic transmission
| Autor: | Matomo Nishio, Kiyonao Sada, Takaharu Ishibashi, Takanobu Taniguchi, Hatsumi Yoshiki, Takayoshi Masuoka, Ikunobu Muramatsu, Kung-Shing Lee, Junsuke Uwada |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Presynaptic Terminals Synaptic Transmission Biochemistry Choline 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Organ Culture Techniques 0302 clinical medicine Postsynaptic potential Acetylcholine transport Muscarinic acetylcholine receptor medicine Animals Rats Wistar Acetylcholine receptor Tetraethylammonium Biological Transport Long-term potentiation Hemicholinium 3 Acetylcholine Cholinergic Neurons Corpus Striatum Rats 030104 developmental biology chemistry Synapses Biophysics Cholinergic 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Journal of Neurochemistry. 143:76-86 |
| ISSN: | 0022-3042 |
| DOI: | 10.1111/jnc.14127 |
| Popis: | In addition to hydrolysis by acetylcholine esterase (AChE), acetylcholine (ACh) is also directly taken up into brain tissues. In this study, we examined whether the uptake of ACh is involved in the regulation of synaptic ACh concentrations. Superfusion experiments with rat striatal segments pre-incubated with [3 H]choline were performed using an ultra-mini superfusion vessel, which was developed to minimize superfusate retention within the vessel. Hemicholinium-3 (HC-3) at concentrations less than 1 μM, selectively inhibited the uptake of [3 H]choline by the high affinity-choline transporter 1 and had no effect on basal and electrically evoked [3 H]efflux in superfusion experiments. In contrast, HC-3 at higher concentrations, as well as tetraethylammonium (>10 μM), which inhibited the uptake of both [3 H]choline and [3 H]ACh, increased basal [3 H]overflow and potentiated electrically evoked [3 H]efflux. These effects of HC-3 and tetraethylammonium were also observed under conditions where tissue AChE was irreversibly inactivated by diisopropylfluorophosphate. Specifically, the potentiation of evoked [3 H]efflux was significantly higher in AChE-inactivated preparations and was attenuated by atropine. On the other hand, striatal segments pre-incubated with [3 H]ACh failed to increase [3 H]overflow in response to electrical stimulation. These results show that synaptic ACh concentrations are significantly regulated by the postsynaptic uptake of ACh, as well as by AChE hydrolysis and modulation of ACh release mediated through presynaptic muscarinic ACh receptors. In addition, these data suggest that the recycling of ACh-derived choline may be minor in cholinergic terminals. This study reveals a new mechanism of cholinergic transmission in the central nervous system. |
| Databáze: | OpenAIRE |
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