Abstract
Adenosine is a signaling molecule and downstream product of ATP that acts as a neuromodulator. Adenosine regulates physiological processes, such as neurotransmission and blood flow, on a time scale of minutes to hours. Recent developments in electrochemical techniques, including fast-scan cyclic voltammetry (FSCV), have allowed direct detection of adenosine with sub-second temporal resolution. FSCV studies have revealed a novel mode of rapid signaling that lasts only a few seconds. This rapid release of adenosine can be evoked by electrical or mechanical stimulations or it can be observed spontaneously without stimulation. Adenosine signaling on this time scale is activity dependent; however, the mode of release is not fully understood. Rapid adenosine release modulates oxygen levels and evoked dopamine release, indicating that adenosine may have a rapid modulatory role. In this review, we outline how FSCV can be used to detect adenosine release, compare FSCV with other techniques used to measure adenosine, and present an overview of adenosine signaling that has been characterized using FSCV. These studies point to a rapid mode of adenosine modulation, whose mechanism and function will continue to be characterized in the future.
Highlights
Comparison of Microdialysis and Fast-scan cyclic voltammetry (FSCV)Microdialysis is one of the most general techniques for monitoring neurochemical changes
Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes directly measures adenosine on a sub-second time scale [18,19], with a sampling rate of 10 times per second
We examine the fundamental principles of adenosine detection by FSCV, compare it to other measurement techniques, and highlight the biological applications and possible future studies that rapid measurements with FSCV may enable
Summary
Microdialysis is one of the most general techniques for monitoring neurochemical changes. A microdialysis probe is inserted into the brain and artificial cerebral spinal fluid is pumped through the probe. The aliquot is usually analyzed with HPLC and one advantage is that many species can be measured from the same sample [41]. The limit of detection for adenosine was as low as 5 nM using microdialysis [43]. Microdialysis monitoring has revealed that adenosine is released during ischemia and built up in 15 min [44]. Microdialysis samples were collected for 5 to 10 min, so the time scale of the measurement is slower than FSCV. Microdialysis is good for studying slower changes in basal levels of adenosine while FSCV is better at detecting rapid fluctuations in extracellular adenosine
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