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

<p><b>A).</b> 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 (<i>P</i>_<i>Mut</i>), at 20mM glucose, with <i>g</i>_<i>coup</i> = 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>B).</b> Fraction of cells showing significant [Ca²⁺] elevations for simulations of diazoxide application uniformly in all cells (<i>α</i>) at 11mM glucose, <i>P</i>_<i>mu</i>t = 1, with <i>g</i>_<i>coup</i> as in A. Inset represents islet where cells show variable K_ATP activity modelling intrinsic heterogeneity (green). <b>C).</b> Representative time courses from simulations with increased <i>k</i>^<i>’</i>_<i>1/2</i> values (reduced ATP-sensitivity) as indicated, far left for <i>g</i>_<i>coup</i> = 120pS. <b>D).</b> As in C for <i>g</i>_<i>coup</i> = 50pS. <b>E).</b> As in C for <i>g</i>_<i>coup</i> = 0pS. Scale bars represent 20% increase in simulated [Ca²⁺]. <b>F).</b> Fraction of cells showing significant [Ca²⁺] elevations for increased <i>k</i>^<i>’</i>_<i>1/2</i> values uniformly in all cells at 11mM glucose, <i>P</i>_<i>mu</i>t = 1, for <i>g</i>_<i>coup</i> = 120pS (black), 50pS (blue), 20pS (purple), 10pS (green), and 0pS (red). <b>G).</b> Mean [Ca²⁺] duty cycle for increased <i>k</i>^<i>’</i>_<i>1/2</i> values as in F. <b>H).</b> <i>k</i>^<i>’</i>_<i>1/2</i> value at which 50% of cells show significant [Ca²⁺] elevations for values of <i>g</i>_<i>coup</i> over 5 simulated islets. <b>I).</b> Mean±SD cell parameters for active and inactive cells at <i>g</i>_<i>coup</i> = 0pS for simulations in A (<i>P</i>_<i>mut</i>), B (<i>α</i>), F (<i>k</i>^<i>’</i>_<i>1/2</i>). All data is representative of n = 5 simulations with different random number seeds.