Upregulation of an inward rectifying K+ channel can rescue slow Ca2+ oscillations in K(ATP) channel deficient pancreatic islets
Fig 11
Fura-2 Ca2+ measurements of SUR1-/- and wild-type islets compared with model simulations.
In the experiments, the change in Ca2+ is expressed as the fura-2 340/380 fluorescence ratio. (A) In the Kir2.1 model, the parameter kSERCA is reduced by a factor of 4 to mimic application of the SERCA pump blocker thapsigargin (TG). (B) Fura-2 Ca2+ measurements from 3 representative SUR1-/- islets. Islets were maintained in 11 mM glucose, and the irreversible SERCA pump blocker TG was applied as indicated. Slow Ca2+ oscillations persisted after TG application in all 10 KO islets tested, as predicted by the model. (C) In the wild-type model, parameter kSERCA was reduced by a factor of 4 to simulate TG application. D) Fura-2 Ca2+ measurements from 3 representative wild-type islets maintained in 11 mM glucose. TG was applied as indicated. Slow Ca2+ oscillations were replaced by sustained elevation in Ca2+ reflecting continuous spiking or fast bursting in 13 of 14 wild-type islets tested, as predicted.