Fig 3. Simulated dependence of islet [Ca²⁺] on electrical coupling upon reduced K_ATP ATP sensitivity.

A). Quantification of [Ca²⁺], as expressed by the fraction of cells showing significant [Ca²⁺] elevations, for simulations of Kir6.2^{[ΔN30,K185Q]} expression in a percentage of cells (P_Mut), at 20mM glucose, with g_coup = 120pS (black), 50pS (blue), and 0pS (red). Inset represents islet where specific cells show increased K_ATP activity modelling mosaic Kir6.2^{[ΔN30,K185Q]} expression (green). B). Fraction of cells showing significant [Ca²⁺] elevations for simulations of diazoxide application uniformly in all cells (α) at 11mM glucose, P_mut = 1, with g_coup as in A. Inset represents islet where cells show variable K_ATP activity modelling intrinsic heterogeneity (green). C). Representative time courses from simulations with increased k^’_1/2 values (reduced ATP-sensitivity) as indicated, far left for g_coup = 120pS. D). As in C for g_coup = 50pS. E). As in C for g_coup = 0pS. Scale bars represent 20% increase in simulated [Ca²⁺]. F). Fraction of cells showing significant [Ca²⁺] elevations for increased k^’_1/2 values uniformly in all cells at 11mM glucose, P_mut = 1, for g_coup = 120pS (black), 50pS (blue), 20pS (purple), 10pS (green), and 0pS (red). G). Mean [Ca²⁺] duty cycle for increased k^’_1/2 values as in F. H). k^’_1/2 value at which 50% of cells show significant [Ca²⁺] elevations for values of g_coup over 5 simulated islets. I). Mean±SD cell parameters for active and inactive cells at g_coup = 0pS for simulations in A (P_mut), B (α), F (k^’_1/2). All data is representative of n = 5 simulations with different random number seeds.