Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Tuesday Speaker Abstracts

RAPID ELECTROCHEMICAL MEASURE OF NEUROTRANSMITTER DYNAMICS IN A BEATING PIG HEART

Corey Smith 1 ; Sarah Hickle 1 ; Jeffrey Ardell 2 ; Shyue-An Chan 1 ; 1 Case Western Reserve University, Physiology and Biophysics, Cleveland, OH, USA 2 UCLA, Cardiac Arrhythmia Center, Los Angeles, CA, USA

Sympathetic control of regional cardiac function occurs through postganglionic sympathetic innervation from stellate ganglia. Norepinephrine (NE) is the primary neurotransmitter released from postganglionic efferent nerves and increases cardiac contractility. Neuropeptide Y (NPY) is an abundant cardiac co-transmitter released from the same efferent nerves under intense activation. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, and cardiac remodeling. Chronic elevated sympathetic stress, resulting in increased NE and NPY release, has been implicated in the pathogenesis of several cardiovascular disorders including hypertension, myocardial infarction, heart failure, and arrhythmias, which may result in sudden cardiac death. The ability to measure neurotransmitters and neuropeptides in vivo that are relevant to the assessment of disease progression is of great interest to the scientific and medical communities. The current methods to determent these neurotransmitters can take several days or weeks to obtain, as they can be limited in resolution both spatially and temporally (e.g., fluid compartment microdialysis of interstitial fluid analyzed by enzyme-linked immunosorbent assay [ELISA], high-performance liquid chromatography [HPLC], or mass spectrometry); thus, their guidance of timely diagnosis and treatment is disrupted. In the present study, a novel adaptation of an electrochemical detection of NE levels at high spatial and temporal resolution in vivo is presented. NPY levels are detected in vivo through the use of a capacitive immunoprobe biosensor. The fabrication protocol and in vitro characterization of these probes are described and measurements of sympathetic stimulation-evoked NE and NPY release in vivo are provided. Our data demonstrate an approach for the fast and localized measurement of neuropeptides in both tissue and circulation. Future applications include intraoperative real-time assessment of disease progression and minimally invasive catheter-based deployment of these probes.

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