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Calcium Modulation of Exocytosis-Linked Plasma Membrane Potential Oscillations in INS-1 832/13 Cells.

Gerencser, Akos A; Mulder, Hindrik LU and Nicholls, David G (2015) In Biochemical Journal 471(1). p.111-122
Abstract
In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψp) leading to associated fluctuations in cytosolic free Ca(2+) concentration ([Ca(2+)]c). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the nature of the oscillator, with simultaneous fluorescence monitoring of Δψp, [Ca(2+)]c and exocytosis at single cell resolution, combined with analysis of the occurrence, frequency and amplitude of Δψp oscillations. Oscillations were closely coupled to exocytosis, indicated by coincident synaptopHluorin fluorescence enhancement. L-type Ca(2+) channel... (More)
In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψp) leading to associated fluctuations in cytosolic free Ca(2+) concentration ([Ca(2+)]c). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the nature of the oscillator, with simultaneous fluorescence monitoring of Δψp, [Ca(2+)]c and exocytosis at single cell resolution, combined with analysis of the occurrence, frequency and amplitude of Δψp oscillations. Oscillations were closely coupled to exocytosis, indicated by coincident synaptopHluorin fluorescence enhancement. L-type Ca(2+) channel inhibitors enhanced Δψp and [Ca(2+)]c oscillation frequency in the presence of pyruvate, but abolished the sustained [Ca(2+)]c response following KCl-depolarization. The L-type Ca(2+) channel inhibitor isradipine did not inhibit oscillation-linked exocytosis. The T-type Ca(2+) channel inhibitor NNC-55 0396 inhibited Δψp and [Ca(2+)]c oscillations, implying that T-channels trigger oscillations and consequent exocytosis.Since distinct ion channels operate in oscillating and non-oscillating cells, quantitative analysis of Δψp and [Ca(2+)]c oscillations in a β-cell population may help to improve our understanding of the link between metabolism and insulin secretion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical Journal
volume
471
issue
1
pages
111 - 122
publisher
Portland Press Limited
external identifiers
  • pmid:26243883
  • wos:000369168000010
  • scopus:84942354220
ISSN
0264-6021
DOI
10.1042/BJ20150616
language
English
LU publication?
yes
id
340c14ec-a857-4b81-8503-64e619a35121 (old id 7844694)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26243883?dopt=Abstract
date added to LUP
2015-09-05 13:18:49
date last changed
2017-08-27 03:16:59
@article{340c14ec-a857-4b81-8503-64e619a35121,
  abstract     = {In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψp) leading to associated fluctuations in cytosolic free Ca(2+) concentration ([Ca(2+)]c). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the nature of the oscillator, with simultaneous fluorescence monitoring of Δψp, [Ca(2+)]c and exocytosis at single cell resolution, combined with analysis of the occurrence, frequency and amplitude of Δψp oscillations. Oscillations were closely coupled to exocytosis, indicated by coincident synaptopHluorin fluorescence enhancement. L-type Ca(2+) channel inhibitors enhanced Δψp and [Ca(2+)]c oscillation frequency in the presence of pyruvate, but abolished the sustained [Ca(2+)]c response following KCl-depolarization. The L-type Ca(2+) channel inhibitor isradipine did not inhibit oscillation-linked exocytosis. The T-type Ca(2+) channel inhibitor NNC-55 0396 inhibited Δψp and [Ca(2+)]c oscillations, implying that T-channels trigger oscillations and consequent exocytosis.Since distinct ion channels operate in oscillating and non-oscillating cells, quantitative analysis of Δψp and [Ca(2+)]c oscillations in a β-cell population may help to improve our understanding of the link between metabolism and insulin secretion.},
  author       = {Gerencser, Akos A and Mulder, Hindrik and Nicholls, David G},
  issn         = {0264-6021},
  language     = {eng},
  number       = {1},
  pages        = {111--122},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Calcium Modulation of Exocytosis-Linked Plasma Membrane Potential Oscillations in INS-1 832/13 Cells.},
  url          = {http://dx.doi.org/10.1042/BJ20150616},
  volume       = {471},
  year         = {2015},
}