title: Is bursting more effective than spiking in evoking pituitary hormone secretion? A spatiotemporal simulation study of calcium and granule dynamics.
abstract: Endocrine cells of the pituitary gland secrete a number of hormones, and the amount of hormone released by a cell is controlled in large part by the cell's electrical activity and subsequent Ca(2+) influx. Typical electrical behaviors of pituitary cells include continuous spiking and so-called pseudo-plateau bursting. It has been shown that the amplitude of Ca(2+) fluctuations is greater in bursting cells, leading to the hypothesis that bursting cells release more hormone than spiking cells. In this work, we apply computer simulations to test this hypothesis. We use experimental recordings of electrical activity as input to mathematical models of Ca(2+) channel activity, buffered Ca(2+) diffusion, and Ca(2+)-driven exocytosis. To compare the efficacy of spiking and bursting on the same cell, we pharmacologically block the large-conductance potassium (BK) current from a bursting cell or add a BK current to a spiking cell via dynamic clamp. We find that bursting is generally at least as effective as spiking at evoking hormone release and is often considerably more effective, even when normalizing to Ca(2+) influx. Our hybrid experimental/modeling approach confirms that adding a BK-type K(+) current, which is typically associated with decreased cell activity and reduced secretion, can actually produce an increase in hormone secretion, as suggested earlier.
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy;
authors.forename: Alessia
authors.initials: A
authors.lastname: Tagliavini
authors.affiliation: Department of Mathematics and Program in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida; and Exeter University Medical School, Biomedical Neuroscience, Exeter, United Kingdom.
authors.forename: Joël
authors.initials: J
authors.lastname: Tabak
authors.affiliation: Department of Mathematics and Program in Neuroscience and Molecular Biophysics, Florida State University, Tallahassee, Florida; and.
authors.forename: Richard
authors.initials: R
authors.lastname: Bertram
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy; pedersen@dei.unipd.it.
authors.forename: Morten Gram
authors.identifier: http://orcid.org/0000-0002-2639-2394
authors.initials: MG
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D003198:Computer Simulation; D005089:Exocytosis; D052681:Gonadotrophs / Q000378:metabolism*; D052682:Lactotrophs / Q000378:metabolism*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008962:Models, Theoretical; D018408:Patch-Clamp Techniques; D010907:Pituitary Hormones / Q000378:metabolism*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D052683:Somatotrophs / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010907:Pituitary Hormones; D002118:Calcium
keywords: Ca2+ oscillations; dynamic clamp; electrical activity; exocytosis; mathematical modeling