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

Patch-clamp and capacitance measurements were applied to α-, β- and δ-cells in intact mouse pancreatic islets. The maximum rate of β-cell exocytosis during a depolarization to 0 mV was 14 granules/s, <5% of that observed in isolated β-cells. β-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 β-cell depends on Ca2+-influx via L-type Ca2+-channels, whereas N-type Ca2+-channels are important in α-cells. δ-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 Ca2+-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 δ-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 β-cell is electrically coupled to seven other β-cells. Coupling is sufficient to account for the synchronization and propagation of the cytosolic Ca2+-oscillations but small changes in β-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.

Grantor dc:publisher

Department of Clinical Sciences, Lund University

Year dc:date

2008

Author dc:creator

• Zhang, Quan

• Endocrinology and Diabetes

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Identifier

urn:isbn:978-91-85897-78-0

OAI identifier oai:identifier

oai:lup.lub.lu.se:3a617885-2a27-475b-88df-c6e19514eb48