Regulation of synaptic acetylcholine concentrations by acetylcholine transport in rat striatal cholinergic transmission

This is the authors' abstract. We don't add key points for this paper.

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 ofACh is involved in the regulation of synapticACh concentrations. Superfusion experiments with rat striatal segments pre‐incubated with [3H]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 [3H]choline by the high affinity‐choline transporter 1 and had no effect on basal and electrically evoked [3H]efflux in superfusion experiments. In contrast,HC‐3 at higher concentrations, as well as tetraethylammonium (>10 μM), which inhibited the uptake of both [3H]choline and [3H]ACh, increased basal [3H]overflow and potentiated electrically evoked [3H]efflux. These effects ofHC‐3 and tetraethylammonium were also observed under conditions where tissueAChE was irreversibly inactivated by diisopropylfluorophosphate. Specifically, the potentiation of evoked [3H]efflux was significantly higher inAChE‐inactivated preparations and was attenuated by atropine. On the other hand, striatal segments pre‐incubated with [3H]ACh failed to increase [3H]overflow in response to electrical stimulation. These results show that synapticACh concentrations are significantly regulated by the postsynaptic uptake ofACh, as well as byAChE hydrolysis and modulation ofACh release mediated through presynaptic muscarinicACh receptors. In addition, these data suggest that the recycling ofACh‐derived choline may be minor in cholinergic terminals. This study reveals a new mechanism of cholinergic transmission in the central nervous system.