Catecholamine Release and Transport in the Adrenal Gland

Isolated chromaffin cells have been extensively studied as model neuronal cells. These studies have revealed a plethora of information regarding the last stage of stimulussecretion coupling or exocytosis. However, preparations of isolated chromaffin cells lack the ability to communicate and exhibit a number of phenotypic modifications that render them functionally different from their physiological counterparts. It is therefore highly desirable to probe the secretory process of exocytosis in a preparation that mimics in vivo conditions more accurately. Adrenal tissue slices are starting to become the preparation of choice for exocytotic studies. The morphological architecture of the adrenal gland and the timescale of exocytotic events necessitate a detection method that has both temporal and spatial resolution to accurately examine chemical messenger dynamics. Electroanalytical techniques, in particular fast-scan cyclic voltammetry and constant-potential amperometry, at carbon-fiber microelectrodes satisfy both of the detection requirements and also offer exquisite selectivity for electroactive chemical messengers. This dissertation focuses on explorations of catecholamine exocytosis in the intact adrenal gland. The small size of the carbon-fiber microsensor was exploited in detailed investigations of catecholamine dynamics within various adrenomedullary compartments. Constant-potential amperometry was utilized in the pursuit of the underlying causes of unexpected spontaneous catecholamine transients. Additionally, the balance between exocytotic release and clearance of catecholamines from the extracellular space was studied by employing fast-scan cyclic voltammetry. Finally, electrical stimulation parameters were varied to determine the conditions resulting in the most efficacious and least damaging electrical stimulation. The findings in this work offer the first real-time overview of the fate of catecholamines as they traverse various adrenomedullary compartments on their journey to the blood stream