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Cell coupling in mouse pancreatic beta-cells measured in intact islets of Langerhans

Zhang, Quan ; Galvanovskis, Juris ; Abdulkader, Fernando ; Partridge, Christopher J. ; Gopel, Sven O. ; Eliasson, Lena LU orcid and Rorsman, Patrik (2008) In Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Science 366(1880). p.3503-3523
Abstract
The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified beta-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent beta-cells. Using a combination of current- and voltage-clamp recordings, the total gap junctional conductance between beta-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell ( due to the. ring of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of beta-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to -55 mV) gave rise to a slow capacitive current indicative of coupling between beta-cells, but not in... (More)
The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified beta-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent beta-cells. Using a combination of current- and voltage-clamp recordings, the total gap junctional conductance between beta-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell ( due to the. ring of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of beta-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to -55 mV) gave rise to a slow capacitive current indicative of coupling between beta-cells, but not in non-beta-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial beta-cell in an islet is in electrical contact with six to seven other beta-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell K-ATP channel conductance (G(K,ATP)) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC50 of approximately 4 mM. Theoretical considerations indicate that the coupling between beta-cells within the islet is sufficient to allow propagation of [Ca2+](i) waves to spread with a speed of approximately 80 mu m s(-1), similar to that observed experimentally in confocal [Ca2+](i) imaging. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
K-ATP, gap junctions, cell coupling, beta-cell, pancreatic islets, channels
in
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Science
volume
366
issue
1880
pages
3503 - 3523
publisher
Royal Society Publishing
external identifiers
  • wos:000258866400005
  • scopus:51049110095
  • pmid:18632454
ISSN
1364-503X
DOI
10.1098/rsta.2008.0110
language
English
LU publication?
yes
id
42b86dad-a5f2-4778-b43c-350eb05b3092 (old id 1247634)
date added to LUP
2016-04-01 14:08:44
date last changed
2022-01-27 23:01:17
@article{42b86dad-a5f2-4778-b43c-350eb05b3092,
  abstract     = {{The perforated whole-cell configuration of the patch-clamp technique was applied to functionally identified beta-cells in intact mouse pancreatic islets to study the extent of cell coupling between adjacent beta-cells. Using a combination of current- and voltage-clamp recordings, the total gap junctional conductance between beta-cells in an islet was estimated to be 1.22 nS. The analysis of the current waveforms in a voltage-clamped cell ( due to the. ring of an action potential in a neighbouring cell) suggested that the gap junctional conductance between a pair of beta-cells was 0.17 nS. Subthreshold voltage-clamp depolarization (to -55 mV) gave rise to a slow capacitive current indicative of coupling between beta-cells, but not in non-beta-cells, with a time constant of 13.5 ms and a total charge movement of 0.2 pC. Our data suggest that a superficial beta-cell in an islet is in electrical contact with six to seven other beta-cells. No evidence for dye coupling was obtained when cells were dialysed with Lucifer yellow even when electrical coupling was apparent. The correction of the measured resting conductance for the contribution of the gap junctional conductance indicated that the whole-cell K-ATP channel conductance (G(K,ATP)) falls from approximately 2.5 nS in the absence of glucose to 0.1 nS at 15 mM glucose with an estimated IC50 of approximately 4 mM. Theoretical considerations indicate that the coupling between beta-cells within the islet is sufficient to allow propagation of [Ca2+](i) waves to spread with a speed of approximately 80 mu m s(-1), similar to that observed experimentally in confocal [Ca2+](i) imaging.}},
  author       = {{Zhang, Quan and Galvanovskis, Juris and Abdulkader, Fernando and Partridge, Christopher J. and Gopel, Sven O. and Eliasson, Lena and Rorsman, Patrik}},
  issn         = {{1364-503X}},
  keywords     = {{K-ATP; gap junctions; cell coupling; beta-cell; pancreatic islets; channels}},
  language     = {{eng}},
  number       = {{1880}},
  pages        = {{3503--3523}},
  publisher    = {{Royal Society Publishing}},
  series       = {{Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Science}},
  title        = {{Cell coupling in mouse pancreatic beta-cells measured in intact islets of Langerhans}},
  url          = {{http://dx.doi.org/10.1098/rsta.2008.0110}},
  doi          = {{10.1098/rsta.2008.0110}},
  volume       = {{366}},
  year         = {{2008}},
}