"Switching off activity in minimal three-cell topologies of coupled heterogenous beta cells"
Beta cells are cells in the pancreas that produce and release insulin in response to blood glucose levels. Interactions between beta cells within their local network of an islet is important for the regulation of insulin secretion and to enhance the glucose stimulated response. Beta cells are coupled through gap junctions and generate synchronous threshold-based oscillations of their membrane potential. Dysfunction of coupling has been associated with diabetes. Experiments have suggested individual beta cells can control synchronization. We have previously shown in specific conditions a 'switch' cell can serve this purpose. However, the cellular and network conditions are not fully understood. To test a minimal model representation of this behavior we use a mathematical model of bursting in two triplet configurations, chain and triangle. Biological heterogeneity is introduced by varying the gap junctional coupling and the rate of calcium extrusion parameters for each of the cells, which permits varying types of frequencies. We measure the amplitude of a patched steady cell, and we investigate how the bursting of a high frequency cell and coupling can lead to change of the behavior of the patched steady cell. To demonstrate a switch cell exists, we effect the second intermediate frequency cell by (a) silencing it setting the voltage to rest or (b) ablating it disconnecting this cell from other cells, and observe under what conditions there is a loss of activity. We have found the range of coupling strength and calcium extrusion parameters that support switch cell behavior in the simplified system.