Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice.
BACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of β-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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3071710?pdf=render |
| _version_ | 1811321951700910080 |
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| author | Zuheng Ma Catharina Lavebratt Malin Almgren Neil Portwood Lars E Forsberg Robert Bränström Erik Berglund Sture Falkmer Frank Sundler Nils Wierup Anneli Björklund |
| author_facet | Zuheng Ma Catharina Lavebratt Malin Almgren Neil Portwood Lars E Forsberg Robert Bränström Erik Berglund Sture Falkmer Frank Sundler Nils Wierup Anneli Björklund |
| author_sort | Zuheng Ma |
| collection | DOAJ |
| description | BACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of β-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 wild-type mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the β-cell population and also to α- and δ-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 β-cells. This duration effect on action potential in β-cells from mceph/mceph mice was mimicked by dendrotoxin-K in β-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 β-cells of several species, and these channels can influence glucose-stimulated insulin release. |
| first_indexed | 2024-04-13T13:26:37Z |
| format | Article |
| id | doaj.art-e295ca21d54b49e1a428fd1ebc35b673 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T13:26:37Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e295ca21d54b49e1a428fd1ebc35b6732022-12-22T02:45:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1821310.1371/journal.pone.0018213Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice.Zuheng MaCatharina LavebrattMalin AlmgrenNeil PortwoodLars E ForsbergRobert BränströmErik BerglundSture FalkmerFrank SundlerNils WierupAnneli BjörklundBACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of β-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 wild-type mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the β-cell population and also to α- and δ-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 β-cells. This duration effect on action potential in β-cells from mceph/mceph mice was mimicked by dendrotoxin-K in β-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 β-cells of several species, and these channels can influence glucose-stimulated insulin release.http://europepmc.org/articles/PMC3071710?pdf=render |
| spellingShingle | Zuheng Ma Catharina Lavebratt Malin Almgren Neil Portwood Lars E Forsberg Robert Bränström Erik Berglund Sture Falkmer Frank Sundler Nils Wierup Anneli Björklund Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. PLoS ONE |
| title | Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. |
| title_full | Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. |
| title_fullStr | Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. |
| title_full_unstemmed | Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. |
| title_short | Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice. |
| title_sort | evidence for presence and functional effects of kv1 1 channels in β cells general survey and results from mceph mceph mice |
| url | http://europepmc.org/articles/PMC3071710?pdf=render |
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