MODULATION OF ACETYLCHOLINE-RELEASE FROM RAT STRIATAL SLICES - INTERACTION BETWEEN 4-AMINOPYRIDINE AND ATROPINE

The objective of these studies was to determine whether the muscarinic receptor-mediated autoregulation of the basal release of acetylcholine (ACh), like the modulation of evoked release, involves 4-aminopyridine (4-AP)-sensitive potassium channels. To accomplish this, striatal and hippocampal slices were incubated with 4-AP in the absence or presence of atropine, and the release of ACh was measured. 4-AP increased the release of ACh in a concentration-dependent manner; a maximal effect (280% of control release) was achieved in the presence of 100-mu-M. The maximal release of ACh from hippocampal slices was approximately 150% of control release and was achieved in the presence of a broad range of concentrations (33-333-mu-M 4-AP). Tetrodotoxin (1-mu-M) totally abolished the 4-AP-induced release of ACh from hippocampal slices, but only attenuated the 4-AP-induced release from striatal slices, i.e., in the presence of tetrodotoxin, the 4-AP-induced release of ACh from the latter was significantly greater than control release by 54%. Atropine (0.1-mu-M) increased significantly the basal release of ACh from striatal slices by 61%. When striatal slices were incubated with 4-AP in the presence of this maximally effective concentration of atropine, ACh release was significantly greater than release from slices incubated with either atropine or 4-AP alone, suggesting that atropine and 4-AP increase neurotransmitter release by independent mechanisms. Although oxotremorine did not alter either the 4-AP- or atropine-induced release of ACh, it prevented the potentiated response exhibited by slices incubated with both both atropine and 4-AP. When hippocampal slices, which do not exhibit autoregulation of basal ACh release by atropine, were incubated with 4-AP and atropine, the release of ACh did not differ from slices incubated in the presence of 4-AP alone. Results suggest that the muscarinic receptor-mediated regulation of the basal release of ACh from striatal slices differs from the modulation of evoked release and does not involve 4-AP-sensitive potassium channels.