HISTAMINE RELEASE FROM BEIGE MOUSE MAST CELLS

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Mast cells of beige mice present with intracellular secretory granules of approximately 4 microns in diameter. When individual granules fuse with the plasma membrane during exocytosis, the cell surface area increases by 2-8 % for each fusion event (as measured by monitoring plasma membrane capacitance) and the granule diameters increase by 40%. These cells have been used in two independent but related projects. In the first project, these exocytotic pores were studied which form an aqueous pathway between the granule interior and the extracellular medium. The frequency histogram for occurrence of pores of given conductance is broad and independent of the frequency of the stimulating sine wave used to measure capacitance. Furthermore the frequency histogram is similar for two simultaneous but independent measurements of capacitance. In the second project, the physics-chemical nature of granule swelling was studied. Secretory granules generally contain a dehydrated, condensed polymer network or matrix that hydrates and swells upon release. In beige mouse mast cells, relative hydration is dependent upon the constituents of its ionic environment. Divalent cations reduce hydration whereas monovalent cations either have a negligible effect or increase the polymer hydration relative to the effects of distilled water alone. This size is critically dependent upon the solution present at the moment of initial swelling. This variable state behavior may have clinical relevance for Cystic Fibrosis (CF), a genetic disorder in which abnormally thick, dehydrated mucus secretions obstruct airways and pancreatic ducts. If the hydration state of the mucus is also irreversibly dependent on initial extracellular ionic conditions at the time of mucus secretion, then patients with CF may have mucus in an altered state due to the well known alteration in ionic composition of the extracellular composition.