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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4615234
- author
- Pedersen, Morten Gram
LU
; Salunkhe, Vishal Ashok
LU
; Svedin, Emma
LU
; Edlund, Anna
LU
and Eliasson, Lena
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 9
- issue
- 8
- article number
- e103874
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:25105407
- wos:000343231900027
- scopus:84905671646
- pmid:25105407
- 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
- 2016-04-01 14:25:39
- date last changed
- 2024-01-10 03:42:42
@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.}},
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 (PLoS)}},
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 = {{https://lup.lub.lu.se/search/files/3970385/8147023}},
doi = {{10.1371/journal.pone.0103874}},
volume = {{9}},
year = {{2014}},
}