Electrochemical detection of acetylcholine and choline: application to the quantitative nonradiochemical evaluation of choline transport

Abstract

The development of analytical methods for determining the cholinergic biomarkers acetylcholine (ACh) and choline (Ch) is important for assessing their role in neurological and cognitive functions. In this review, electrochemical (EC) strategies to detect ACh and Ch are summarized and compared to other analysis methods. Recent research focusing on the development of a versatile nonradiochemical in vitro assay to evaluate Ch transport is also described. The assay coupled to analysis by capillary electrophoresis (CE) with indirect EC detection at an enzyme-modified microelectrode affords exceptional selectivity and sensitivity. Femtomole or lower mass detection limits for ACh (1 fmol) and Ch (100 amol) have been readily achieved, opening up a new range of possible experiments for investigating transport or turnover of Ch and ACh in neurobiological systems. The value of this method is illustrated through the evaluation of the pharmacological efficacy and mode of inhibition of a new class of quaternary ammonium alkyl-substituted catechol-based inhibitors of high-affinity choline transport (CHT). This microanalytical approach is particularly useful when knowledge of endogenous concentrations of Ch or ACh is desired or when the amount of available compounds or the sample size is limited. A brief description of the principles of CE is also provided.

Ubiquinone-10 in gold-immobilized lipid membrane structures acts as a sensor for acetylcholine and other tetraalkylammonium cations

“…The development of electrochemical acetylcholine sensors is an active research field (e.g. [40,41]), and the system here described represents a rather simple option to carry out the detection of the cation. Further research should be performed in order to develop a working acetylcholine detector and quantificator based on an immobilized lipid membrane structure.…”

Quantification of acetylcholine, an essential neurotransmitter, in brain microdialysis samples by liquid chromatography mass spectrometry

“…In most cases, sensitivity was not suffi cient to be able to detect baseline release of ACh from microdialysates, so that an acetylcholine esterase inhibitor such as neostigmine or physostigmine needed to be added to the perfusion fl uid for adequate quantifi cation. Refer to the recent review on electrochemical detection of ACh (Barkhimer et al 2008). To date, the best sensitivity for ACh assays has been achieved with LC-MS/MS and these MS/MS methodologies have emerged as valuable techniques for neuroscience investigations.…”

Nanopipet-Based Liquid–Liquid Interface Probes for the Electrochemical Detection of Acetylcholine, Tryptamine, and Serotonin via Ionic Transfer

“…Electrochemical detection of nonredox active neurotransmitters (e.g., ACh) is achieved indirectly using an electrode modified with enzyme, where a combination of acetylcholine esterase and choline oxidase is needed and the kinetics of the enzyme reaction can limit the electrode response. 24–27 Methods for direct detection of nonredox active neurotransmitters (e.g., without electrode modification) need to be developed.…”