title: Evidence for presence and functional effects of Kv1.1 channels in β-cells: general survey and results from mceph/mceph mice.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Kv1.1 channels are expressed in the β-cells of several species, and these channels can influence glucose-stimulated insulin release.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Zuheng
authors.initials: Z
authors.lastname: Ma
authors.forename: Catharina
authors.initials: C
authors.lastname: Lavebratt
authors.forename: Malin
authors.initials: M
authors.lastname: Almgren
authors.forename: Neil
authors.initials: N
authors.lastname: Portwood
authors.forename: Lars E
authors.initials: LE
authors.lastname: Forsberg
authors.forename: Robert
authors.initials: R
authors.lastname: Bränström
authors.forename: Erik
authors.initials: E
authors.lastname: Berglund
authors.forename: Sture
authors.initials: S
authors.lastname: Falkmer
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
authors.forename: Anneli
authors.initials: A
authors.lastname: Björklund
mesh_terms: D000200:Action Potentials; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003625:Data Collection; D005260:Female; D016257:Fura-2 / Q000378:metabolism; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051662:Kv1.1 Potassium Channel / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D057054:Molecular Imaging; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017384:Sequence Deletion; D051669:Shab Potassium Channels / Q000378:metabolism; D013045:Species Specificity
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D051669:Shab Potassium Channels; D051662:Kv1.1 Potassium Channel; D016257:Fura-2