Simulations predicting how intrinsic frequency of cells contributes to islet frequency.
A). Schematic of frequency across simulated islet with 25% variation in GK activity. B). Representative time courses of [Ca2+] for 9 cells in simulated islet in A in a simulation with full (120pS) coupling conductance. Blue traces are high frequency cells, Grey are cells with frequency near average frequency, red traces are low frequency cells. C). Same cells as in B but showing [Ca2+] time courses from an uncoupled simulation (0pS coupling conductance). D). Average intrinsic oscillation frequencies of all cells, top 1% or 10% of high frequency cells, or low frequency cells when re-simulated in the absence of gap junction coupling. E). Phase lag from islet average of top 1% or 10% of low frequency, high frequency, or random cells. F). Average kglc from all cells, high frequency cells, or low frequency cells across simulated islet (normalized to average kglc). G). Average frequency of islet when indicated populations of cells are removed from the simulated islet. H). Change in frequency of islet with indicated populations removed with respect to control islet with all cells present. I). Change in frequency when high frequency cells are removed compared to average oscillation frequency of remaining cells that indicates the expected oscillation frequency. J). Same as I. but for simulations where low frequency cells are removed. Error bars are mean ± s.e.m. Repeated measures one-way ANOVA with Tukey post-hoc analysis was performed for simulations in D-H and a Student’s paired t-test was performed for I and J to test for significance. Significance values: ns indicates not significant (p>.05), * indicates significant difference (p < .05), ** indicates significant difference (p < .01), *** indicates significant difference (p < .001), **** indicates significant difference (p < .0001). Data representative of 5 simulations with differing random number seeds. Random removal of cells across the islet was used for all simulations where random cells removed is indicated.