Linked Life Data

20643768

Source:http://linkedlifedata.com/resource/pubmed/id/20643768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 18
pubmed:dateCreated
2010-9-16
pubmed:abstractText
Glucose-induced ?-cell action potential (AP) repolarization is regulated by potassium efflux through voltage gated (Kv) and calcium activated (K(Ca)) potassium channels. Thus, ablation of the primary Kv channel of the ?-cell, Kv2.1, causes increased AP duration. However, Kv2.1(-/-) islet electrical activity still remains sensitive to the potassium channel inhibitor tetraethylammonium. Therefore, we utilized Kv2.1(-/-) islets to characterize Kv and K(Ca) channels and their respective roles in modulating the ?-cell AP. The remaining Kv current present in Kv2.1(-/-) ?-cells is inhibited with 5 ?M CP 339818. Inhibition of the remaining Kv current in Kv2.1(-/-) mouse ?-cells increased AP firing frequency by 39.6% but did not significantly enhance glucose stimulated insulin secretion (GSIS). The modest regulation of islet AP frequency by CP 339818 implicates other K(+) channels, possibly K(Ca) channels, in regulating AP repolarization. Blockade of the K(Ca) channel BK with slotoxin increased ?-cell AP amplitude by 28.2%, whereas activation of BK channels with isopimaric acid decreased ?-cell AP amplitude by 30.6%. Interestingly, the K(Ca) channel SK significantly contributes to Kv2.1(-/-) mouse islet AP repolarization. Inhibition of SK channels decreased AP firing frequency by 66% and increased AP duration by 67% only when Kv2.1 is ablated or inhibited and enhanced GSIS by 2.7-fold. Human islets also express SK3 channels and their ?-cell AP frequency is significantly accelerated by 4.8-fold with apamin. These results uncover important repolarizing roles for both Kv and K(Ca) channels and identify distinct roles for SK channel activity in regulating calcium- versus sodium-dependent AP firing.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1469-7793
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
588
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3525-37
pubmed:dateRevised
2011-11-9
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Calcium-activated and voltage-gated potassium channels of the pancreatic islet impart distinct and complementary roles during secretagogue induced electrical responses.
pubmed:affiliation
Deparment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-0615, USA. david.a.jacobson@vanderbilt.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural