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

Zhang, Quan LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:25.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Professor Rupnik, Marjan, Faculty of Medicine University of Maribor
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:25
pages
110 pages
publisher
Department of Clinical Sciences, Lund University
defense location
Medelhavet, Wallnberglab, University Hospital Malmö, S-20502 Malmö,e Sweden
defense date
2008-03-18 13:00
ISSN
1652-8220
ISBN
978-91-85897-78-0
language
English
LU publication?
yes
id
3a617885-2a27-475b-88df-c6e19514eb48 (old id 1024510)
date added to LUP
2008-02-26 11:37:48
date last changed
2016-09-19 08:44:49
@phdthesis{3a617885-2a27-475b-88df-c6e19514eb48,
  abstract     = {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, &lt;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 &lt;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.},
  author       = {Zhang, Quan},
  isbn         = {978-91-85897-78-0},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {110},
  publisher    = {Department of Clinical Sciences, Lund University},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Cell coupling and exocytosis measured in intact mouse pancreatic islets Control of {delta}-cell secretion},
  volume       = {2008:25},
  year         = {2008},
}