TY - JOUR
T1 - Why pancreatic islets burst but single beta cells do not. The heterogeneity hypothesis
AU - Smolen, P.
AU - Rinzel, J.
AU - Sherman, A.
PY - 1993
Y1 - 1993
N2 - Previous mathematical modeling of beta cell electrical activity has involved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel density, and other parameters. We use gap-junctional electrical coupling, with conductances determined by an experimental histogram. We find that, for reasonable parameter distributions, only a small proportion of isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluster of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only with low probability. In large clusters, the dynamics of intracellular calcium compare well with experiments. Also, these clusters possess a dose-response curve of increasing average electrical activity with respect to a glucose-sensing parameter that is sharp when the cluster is coupled, but shallow when the cluster is decoupled into individual cells. This is in agreement with comparative experiments on cells in suspension and islets.
AB - Previous mathematical modeling of beta cell electrical activity has involved single cells or, recently, clusters of identical cells. Here we model clusters of heterogeneous cells that differ in size, channel density, and other parameters. We use gap-junctional electrical coupling, with conductances determined by an experimental histogram. We find that, for reasonable parameter distributions, only a small proportion of isolated beta cells will burst when uncoupled, at any given value of a glucose-sensing parameter. However, a coupled, heterogeneous cluster of such cells, if sufficiently large (approximately 125 cells), will burst synchronously. Small clusters of such cells will burst only with low probability. In large clusters, the dynamics of intracellular calcium compare well with experiments. Also, these clusters possess a dose-response curve of increasing average electrical activity with respect to a glucose-sensing parameter that is sharp when the cluster is coupled, but shallow when the cluster is decoupled into individual cells. This is in agreement with comparative experiments on cells in suspension and islets.
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U2 - 10.1016/S0006-3495(93)81539-X
DO - 10.1016/S0006-3495(93)81539-X
M3 - Article
C2 - 8369400
AN - SCOPUS:0027161335
SN - 0006-3495
VL - 64
SP - 1668
EP - 1680
JO - Biophysical journal
JF - Biophysical journal
IS - 6
ER -