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

• 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.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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