The release of acetylcholine (ACh) elicited by electrical stimulation was investigated in rat brain cortical slices preloaded with3H-choline. Decreasing the [Ca2+]o from 2.5 to 0.3 mM caused a progressive reduction of the evoked release of ACh. 4-Aminopyridine (4AP) or LF14 [(1,1-dimethyl-3-(4-amino-3-pyridyl)], 4×10-5 M doubled the evoked release of ACh when the [Ca2+]o was 2.5 mM and quadrupled it when it was 0.3 mM, to levels higher than those obtained with 2.5 mM [Ca2+]o alone. This indicates that both 4AP and LF14 decrease the Ca2+ requirements for the evoked release of ACh. The findings of this study indicate that LF14 may be suitable for the symptomatic treatment of senile dementia of Alzheimer's type, presumably caused by dysfuntion of cholinergic transmission in the brain.
- [H]acetylcholine release
- cerebral cortex
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience