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Calcium Current Inactivation Rather than Pool Depletion Explains Reduced Exocytotic Rate with Prolonged Stimulation in Insulin-Secreting INS-1 832/13 Cells.

Pedersen, Morten Gram LU ; Salunkhe, Vishal Ashok LU ; Svedin, Emma LU ; Edlund, Anna LU and Eliasson, Lena LU (2014) In PLoS ONE 9(8).
Abstract
Impairment in beta-cell exocytosis is associated with reduced insulin secretion and diabetes. Here we aimed to investigate the dynamics of Ca2+-dependent insulin exocytosis with respect to pool depletion and Ca2+-current inactivation. We studied exocytosis, measured as increase in membrane capacitance (ΔCm), as a function of calcium entry (Q) in insulin secreting INS-1 832/13 cells using patch clamp and mixed-effects statistical analysis. The observed linear relationship between ΔCm and Q suggests that Ca2+-channel inactivation rather than granule pool restrictions is responsible for the decline in exocytosis observed at longer depolarizations. INS-1 832/13 cells possess an immediately releasable pool (IRP) of ∼10 granules and most... (More)
Impairment in beta-cell exocytosis is associated with reduced insulin secretion and diabetes. Here we aimed to investigate the dynamics of Ca2+-dependent insulin exocytosis with respect to pool depletion and Ca2+-current inactivation. We studied exocytosis, measured as increase in membrane capacitance (ΔCm), as a function of calcium entry (Q) in insulin secreting INS-1 832/13 cells using patch clamp and mixed-effects statistical analysis. The observed linear relationship between ΔCm and Q suggests that Ca2+-channel inactivation rather than granule pool restrictions is responsible for the decline in exocytosis observed at longer depolarizations. INS-1 832/13 cells possess an immediately releasable pool (IRP) of ∼10 granules and most exocytosis of granules occurs from a large pool. The latter is attenuated by the calcium-buffer EGTA, while IRP is unaffected. These findings suggest that most insulin release occurs away from Ca2+-channels, and that pool depletion plays a minor role in the decline of exocytosis upon prolonged stimulation. (Less)
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author
organization
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Contribution to journal
publication status
published
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in
PLoS ONE
volume
9
issue
8
publisher
Public Library of Science
external identifiers
  • pmid:25105407
  • wos:000343231900027
  • scopus:84905671646
ISSN
1932-6203
DOI
10.1371/journal.pone.0103874
language
English
LU publication?
yes
id
86d205b1-964f-4b4e-9c1b-21202a2a4f6d (old id 4615234)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25105407?dopt=Abstract
date added to LUP
2014-09-04 18:48:57
date last changed
2017-03-05 03:55:38
@article{86d205b1-964f-4b4e-9c1b-21202a2a4f6d,
  abstract     = {Impairment in beta-cell exocytosis is associated with reduced insulin secretion and diabetes. Here we aimed to investigate the dynamics of Ca2+-dependent insulin exocytosis with respect to pool depletion and Ca2+-current inactivation. We studied exocytosis, measured as increase in membrane capacitance (ΔCm), as a function of calcium entry (Q) in insulin secreting INS-1 832/13 cells using patch clamp and mixed-effects statistical analysis. The observed linear relationship between ΔCm and Q suggests that Ca2+-channel inactivation rather than granule pool restrictions is responsible for the decline in exocytosis observed at longer depolarizations. INS-1 832/13 cells possess an immediately releasable pool (IRP) of ∼10 granules and most exocytosis of granules occurs from a large pool. The latter is attenuated by the calcium-buffer EGTA, while IRP is unaffected. These findings suggest that most insulin release occurs away from Ca2+-channels, and that pool depletion plays a minor role in the decline of exocytosis upon prolonged stimulation.},
  articleno    = {e103874},
  author       = {Pedersen, Morten Gram and Salunkhe, Vishal Ashok and Svedin, Emma and Edlund, Anna and Eliasson, Lena},
  issn         = {1932-6203},
  language     = {eng},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Calcium Current Inactivation Rather than Pool Depletion Explains Reduced Exocytotic Rate with Prolonged Stimulation in Insulin-Secreting INS-1 832/13 Cells.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0103874},
  volume       = {9},
  year         = {2014},
}