Scalene Waveform for Codetection of Guanosine and Adenosine Using Fast-Scan Cyclic Voltammetry

Abstract

Guanosine and adenosine are important neuromodulators in the brain and work in cooperation to mitigate the effects of stroke, traumatic injury, and other neurological events. Both purines can act on slow (minutes to hours) and rapid (milliseconds to seconds) time scales. A guanosine–adenosine interaction has been proposed in which guanosine modulates adenosine levels, and the two work together to control glutamate neurotransmission. Traditional methods to codetect purines, such as HPLC with microdialysis, are robust but lack the temporal resolution necessary to quantify release in real time. Fast-scan cyclic voltammetry (FSCV) has been used to detect guanosine and adenosine independently, but codetection has not been possible. Here, we developed a novel “scalene waveform” to codetect guanosine and adenosine with nanomolar limits of detection in real time with FSCV. The scalene waveform uses a slow rate (100 V/s) on the forward scan and the conventional rate (400 V/s) on the back scan; potentials go from −0.4 to 1.45 V and back to −0.4 V. The scan rates were optimized to increase the separation of the oxidative peaks for guanosine and adenosine. The temporal separation of the primary peaks was increased (4.6 ± 0.1)-fold at the scalene waveform compared to the traditional waveform. Both exogenously applied guanosine and adenosine and endogenous transient release were detected at the scalene waveform in rat-brain slices. We show the first method for codetecting guanosine and adenosine using FSCV, which can be used to study the guanosine–adenosine interaction and better understand their cooperative therapeutic effects.

Subsecond spontaneous catecholamine release in mesenteric lymph node ex vivo

“…FSCV at carbon‐fiber microelectrodes is an electrochemical technique that allows subsecond detection of neurochemical signaling molecules in tissue. It has been extensively used to study dopamine (DA) (Miles, Mundorf, & Wightman, 2002; Stamford, Kruk, & Millar, 1988), norepinephrine (NE) (Park, Takmakov, & Wightman, 2011), epinephrine (Karin et al, 1994), 5‐HT (Abdalla et al., 2017), adenosine (Lee et al 2018), and guanosine (Cryan et al 2019a; 2019b) signaling in the brain. It has also been used to monitor catecholamine signaling in live murine adrenal glands (Petrovic, Walsh, Thornley, Miller, & Wightman, 2010).…”

Multiplexing neurochemical detection with carbon fiber multielectrode arrays using fast-scan cyclic voltammetry

“…Adjusting the waveform leads to enhanced detection by allowing the analyte to sufficiently adsorb onto the CFME surface and prevent electrode fouling. In other instances, a single waveform has been developed to measure two biomolecules concurrently, such as the nucleosides adenosine and guanosine [46,47]. However, a major limitation of the single-channel CFMEs is that only a single waveform can be tested at once.…”

Deep Learning for Voltammetric Sensing in a Living Animal Brain

“…The excellent spatio‐temporal resolution can be jointly fulfilled by fast‐scan cyclic voltammetry (FSCV), in which the chemical signatures of electroactive molecules were measured in the form of a voltammogram [6] . Though typical cyclic voltammograms for most of neurochemicals are overlapped, by applying well‐designed waveforms, certain type of neurochemicals can be reasonably distinguished [7] . Alternatively, coupling FSCV with chemometric techniques could resolve the substances released in living systems from voltammograms to their respective contributor, providing another effective option for multivariate analysis [8] .…”