Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion

Rocio K. Finol-Urdaneta, Maria S. Remedi, Walter Raasch, Stefan Becker, Robert B. Clark, Nina Strüver, Evgeny Pavlov, Colin G. Nichols, Robert J. French, Heinrich Terlau

Research output: Contribution to journalArticle

Abstract

Glucose-stimulated insulin secretion (GSIS) relies on repetitive, electrical spiking activity of the beta cell membrane. Cyclic activation of voltage-gated potassium channels (K v) generates an outward, 'delayed rectifier' potassium current, which drives the repolarizing phase of each spike and modulates insulin release. Although several K v channels are expressed in pancreatic islets, their individual contributions to GSIS remain incompletely understood. We take advantage of a naturally occurring cone-snail peptide toxin, Conkunitzin-S1 (Conk-S1), which selectively blocks K v1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of GSIS. Conk-S1 increases GSIS in isolated rat islets, likely by reducing K v1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that K v1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell K v current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)424-434
Number of pages11
JournalEMBO Molecular Medicine
Volume4
Issue number5
DOIs
StatePublished - May 2012

Fingerprint

Potassium
Insulin
Glucose
Voltage-Gated Potassium Channels
Snails
Cellular Structures
Islets of Langerhans
Hypoglycemia
Type 2 Diabetes Mellitus
Action Potentials
Cell Membrane
Calcium
Peptides
Membranes

Keywords

  • Conkunitzin-S1
  • Electrical signalling
  • GSIS
  • Pancreas
  • Potassium channels

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Finol-Urdaneta, R. K., Remedi, M. S., Raasch, W., Becker, S., Clark, R. B., Strüver, N., ... Terlau, H. (2012). Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion. EMBO Molecular Medicine, 4(5), 424-434. https://doi.org/10.1002/emmm.201200218

Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion. / Finol-Urdaneta, Rocio K.; Remedi, Maria S.; Raasch, Walter; Becker, Stefan; Clark, Robert B.; Strüver, Nina; Pavlov, Evgeny; Nichols, Colin G.; French, Robert J.; Terlau, Heinrich.

In: EMBO Molecular Medicine, Vol. 4, No. 5, 05.2012, p. 424-434.

Research output: Contribution to journalArticle

Finol-Urdaneta, RK, Remedi, MS, Raasch, W, Becker, S, Clark, RB, Strüver, N, Pavlov, E, Nichols, CG, French, RJ & Terlau, H 2012, 'Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion', EMBO Molecular Medicine, vol. 4, no. 5, pp. 424-434. https://doi.org/10.1002/emmm.201200218
Finol-Urdaneta RK, Remedi MS, Raasch W, Becker S, Clark RB, Strüver N et al. Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion. EMBO Molecular Medicine. 2012 May;4(5):424-434. https://doi.org/10.1002/emmm.201200218
Finol-Urdaneta, Rocio K. ; Remedi, Maria S. ; Raasch, Walter ; Becker, Stefan ; Clark, Robert B. ; Strüver, Nina ; Pavlov, Evgeny ; Nichols, Colin G. ; French, Robert J. ; Terlau, Heinrich. / Block of K v1.7 potassium currents increases glucose-stimulated insulin secretion. In: EMBO Molecular Medicine. 2012 ; Vol. 4, No. 5. pp. 424-434.
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