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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/7844694
- author
- Gerencser, Akos A
; Mulder, Hindrik
LU
and Nicholls, David G
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biochemical Journal
- volume
- 471
- issue
- 1
- pages
- 111 - 122
- publisher
- Portland Press
- external identifiers
-
- pmid:26243883
- wos:000369168000010
- scopus:84942354220
- pmid:26243883
- 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
- 2016-04-01 10:14:31
- date last changed
- 2022-04-04 03:47:47
@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}},
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}},
doi = {{10.1042/BJ20150616}},
volume = {{471}},
year = {{2015}},
}