title: Bursting and calcium oscillations in pancreatic beta-cells: specific pacemakers for specific mechanisms.
abstract: Oscillatory phenomenon in electrical activity and cytoplasmic calcium concentration in response to glucose are intimately connected to multiple key aspects of pancreatic β-cell physiology. However, there is no single model for oscillatory mechanisms in these cells. We set out to identify possible pacemaker candidates for burst activity and cytoplasmic Ca(2+) oscillations in these cells by analyzing published hypotheses, their corresponding mathematical models, and relevant experimental data. We found that although no single pacemaker can account for the variety of oscillatory phenomena in β-cells, at least several separate mechanisms can underlie specific kinds of oscillations. According to our analysis, slowly activating Ca(2+)-sensitive K(+) channels can be responsible for very fast Ca(2+) oscillations; changes in the ATP/ADP ratio and in the endoplasmic reticulum calcium concentration can be pacemakers for both fast bursts and cytoplasmic calcium oscillations, and cyclical cytoplasmic Na(+) changes may underlie patterning of slow calcium oscillations. However, these mechanisms still lack direct confirmation, and their potential interactions raises new issues. Further studies supported by improved mathematical models are necessary to understand oscillatory phenomena in β-cell physiology.
authors.affiliation: Dept. of Medicine, MC-1027, Univ. of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA. lfridlia@medicine.bsd.uchicago.edu
authors.forename: L E
authors.initials: LE
authors.lastname: Fridlyand
authors.forename: N
authors.initials: N
authors.lastname: Tamarina
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D005947:Glucose / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008954:Models, Biological; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D005947:Glucose