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

• Published in: PloS one 2011-04, Vol.6 (4), p.e18213
• Main Authors: Ma, Zuheng, Lavebratt, Catharina, Almgren, Malin, Portwood, Neil, Forsberg, Lars E, Bränström, Robert, Berglund, Erik, Falkmer, Sture, Sundler, Frank, Wierup, Nils, Björklund, Anneli
• Format: Article
• Language: English
• Subjects: Blood glucose; Insulin; Pancreatic beta cells
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0018213

Voltage-dependent K.sup.+ channels (Kv) mediate repolarisation of [beta]-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K.sup.+ 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. 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 [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. Kv1.1 channels are expressed in the [beta]-cells of several species, and these channels can influence glucose-stimulated insulin release.