TY - JOUR
T1 - Diffusion of calcium and metabolites in pancreatic islets
T2 - Killing oscillations with a pitchfork
AU - Tsaneva-Atanasova, Krasimira
AU - Zimliki, Charles L.
AU - Bertram, Richard
AU - Sherman, Arthur
N1 - Funding Information:
This work was supported in part by the intramural research program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and in part by National Science Foundation grant No. DMS-0311856 to R.B.
PY - 2006/5
Y1 - 2006/5
N2 - Cell coupling is important for the normal function of the β-cells of the pancreatic islet of Langerhans, which secrete insulin in response to elevated plasma glucose. In the islets, electrical and metabolic communications are mediated by gap junctions. Although electrical coupling is believed to account for synchronization of the islets, the role and significance of diffusion of calcium and metabolites are not clear. To address these questions we analyze two different mathematical models of islet calcium and electrical dynamics. To study diffusion of calcium, we use a modified Morris-Lecar model. Based on our analysis, we conclude that intercellular diffusion of calcium is not necessary for islet synchronization, at most supplementing electrical coupling. Metabolic coupling is investigated with a recent mathematical model incorporating glycolytic oscillations. Bifurcation analysis of the coupled system reveals several modes of behavior, depending on the relative strength of electrical and metabolic coupling. We find that whereas electrical coupling always produces synchrony, metabolic coupling can abolish both oscillations and synchrony, explaining some puzzling experimental observations. We suggest that these modes are generic features of square-wave bursters and relaxation oscillators coupled through either the activation or recovery variable.
AB - Cell coupling is important for the normal function of the β-cells of the pancreatic islet of Langerhans, which secrete insulin in response to elevated plasma glucose. In the islets, electrical and metabolic communications are mediated by gap junctions. Although electrical coupling is believed to account for synchronization of the islets, the role and significance of diffusion of calcium and metabolites are not clear. To address these questions we analyze two different mathematical models of islet calcium and electrical dynamics. To study diffusion of calcium, we use a modified Morris-Lecar model. Based on our analysis, we conclude that intercellular diffusion of calcium is not necessary for islet synchronization, at most supplementing electrical coupling. Metabolic coupling is investigated with a recent mathematical model incorporating glycolytic oscillations. Bifurcation analysis of the coupled system reveals several modes of behavior, depending on the relative strength of electrical and metabolic coupling. We find that whereas electrical coupling always produces synchrony, metabolic coupling can abolish both oscillations and synchrony, explaining some puzzling experimental observations. We suggest that these modes are generic features of square-wave bursters and relaxation oscillators coupled through either the activation or recovery variable.
UR - http://www.scopus.com/inward/record.url?scp=33646198964&partnerID=8YFLogxK
U2 - 10.1529/biophysj.105.078360
DO - 10.1529/biophysj.105.078360
M3 - Article
C2 - 16500973
AN - SCOPUS:33646198964
SN - 0006-3495
VL - 90
SP - 3434
EP - 3446
JO - Biophysical Journal
JF - Biophysical Journal
IS - 10
ER -