Cell coupling and exocytosis measured in intact mouse pancreatic islets Control of {delta}-cell secretion

by Zhang, Quan, PhD

Abstract (Summary)
Patch-clamp and capacitance measurements were applied to ?-, ?- and ?-cells in intact mouse pancreatic islets. The maximum rate of ?-cell exocytosis during a depolarization to 0 mV was 14 granules/s, <5% of that observed in isolated ?-cells. ?-cell exocytosis exhibited bell-shaped voltage dependence and peaked at +20 mV. At physiological membrane potentials (?-20 mV), the maximum rate of release was ~4 granules/s. Exocytosis in ?-cell depends on Ca2+-influx via L-type Ca2+-channels, whereas N-type Ca2+-channels are important in ?-cells. ?-cell exocytosis exhibits a post-stimulation component not observed in the other islet cell types. Ca2+-imaging in conjunction with capacitance measurements revealed that this feature results from Ca2+-induced Ca2+-release (CICR) via ryanodine receptor 3 (RyR3). Both somatostatin release measurements and patch-clamp experiments indicate that R-type Ca??-channels are tightly coupled to CICR. The latency between Ca2+-influx through R-type Ca2+-channels and CICR was <6 ms. However, unlike what is observed in skeletal muscle, where association has been reported to be equally tight, Ca2+-influx is required in the ?-cells and no CICR can be evoked by depolarization alone. Glucose regulates CICR via promoting intracellular Ca2+ sequestration and cAMP/PKA-mediated modulation of RyR3. Electrophysiological analysis of cell coupling in intact islets reveals that every ?-cell is electrically coupled to seven other ?-cells. Coupling is sufficient to account for the synchronization and propagation of the cytosolic Ca2+-oscillations but small changes in ?-cell electrical activity can be predicted to have strong effects on the synchronization which may contribute to the loss of pulsatile insulin secretion in type-2 diabetes.
Bibliographical Information:


School:Lunds universitet

School Location:Sweden

Source Type:Doctoral Dissertation



Date of Publication:01/01/2008

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