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Three Roads to Islet Bursting: Emergent Oscillations in Coupled Phantom Bursters

Charles L. Zimliki ^*  , David Mears  and Arthur Sherman ^*

^* National Institutes of Health, Laboratory of Biological Modeling, Bethesda, Maryland; Uniformed Services University of the Health Sciences, Department of Anatomy, Physiology and Genetics, Bethesda, Maryland; and Johns Hopkins University, Department of Biomedical Engineering, Baltimore, Maryland

Correspondence: Address reprint requests to Dr. Arthur Sherman, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Laboratory of Biological Modeling, Building 12A, Rm. 4007, 12 South Dr. MSC 5621, Bethesda, MD 20892-5621. Tel.: 301-496-4325; Fax: 301-402-0535; E-mail: asherman{at}nih.gov

Glucose-induced membrane potential and Ca²⁺ oscillations in isolated pancreatic ß-cells occur over a wide range of frequencies, from >6/min (fast) to <1/min (slow). However, cells within intact islets generally oscillate with periods of 10–60 s (medium). The phantom bursting concept addresses how ß-cells can generate such a wide range of frequencies. Here, we explore an updated phantom bursting model to determine how heterogeneity in a single parameter can explain both the broad frequency range observed in single cells and the rarity of medium oscillations. We then incorporate the single-cell model into an islet model with parameter heterogeneity. We show that strongly coupled islets must be composed of predominantly medium oscillating single cells or a mixture of fast and slow cells to robustly produce medium oscillations. Surprisingly, we find that this constraint does not hold for moderate coupling, and that robustly medium oscillating islets can arise from populations of single cells that are essentially all slow or all fast. Thus, with coupled phantom bursters, medium oscillating islets can be constructed out of cells that are either all fast, all slow, or a combination of the two.