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Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice

Ma, Zuheng ; Lavebratt, Catharina ; Almgren, Malin ; Portwood, Neil ; Forsberg, Lars E. ; Branstrom, Robert ; Berglund, Erik ; Falkmer, Sture ; Sundler, Frank LU and Wierup, Nils LU , et al. (2011) In PLoS ONE 6(4).
Abstract
Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from... (More)
Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the beta-cell population and also to alpha-and delta-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse beta-cells. This duration effect on action potential in beta-cells from mceph/mceph mice was mimicked by dendrotoxin-K in beta-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. Conclusion/Significance: Kv1.1 channels are expressed in the beta-cells of several species, and these channels can influence glucose-stimulated insulin release. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
6
issue
4
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000289191300012
  • scopus:79953728221
  • pmid:21483673
ISSN
1932-6203
DOI
10.1371/journal.pone.0018213
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuroendocrine Cell Biology (013212008)
id
920bb5ff-4978-4ea1-bcd9-85b172809bf2 (old id 1918247)
date added to LUP
2016-04-01 12:58:24
date last changed
2022-01-27 08:34:57
@article{920bb5ff-4978-4ea1-bcd9-85b172809bf2,
  abstract     = {{Background: Voltage-dependent K+ channels (Kv) mediate repolarisation of beta-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K+ channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. Methodology/Principal Findings: Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wildtype mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the beta-cell population and also to alpha-and delta-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse beta-cells. This duration effect on action potential in beta-cells from mceph/mceph mice was mimicked by dendrotoxin-K in beta-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. Conclusion/Significance: Kv1.1 channels are expressed in the beta-cells of several species, and these channels can influence glucose-stimulated insulin release.}},
  author       = {{Ma, Zuheng and Lavebratt, Catharina and Almgren, Malin and Portwood, Neil and Forsberg, Lars E. and Branstrom, Robert and Berglund, Erik and Falkmer, Sture and Sundler, Frank and Wierup, Nils and Bjorklund, Anneli}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Evidence for Presence and Functional Effects of Kv1.1 Channels in beta-Cells: General Survey and Results from mceph/mceph Mice}},
  url          = {{https://lup.lub.lu.se/search/files/3078194/1939366.pdf}},
  doi          = {{10.1371/journal.pone.0018213}},
  volume       = {{6}},
  year         = {{2011}},
}