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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Calcium Modulation of Exocytosis-Linked Plasma Membrane Potential Oscillations in INS-1 832/13 Cells.

Author

  • Akos A Gerencser
  • Hindrik Mulder
  • David G Nicholls

Summary, in English

In the presence of high glucose or pyruvate, INS-1 832/13 insulinoma cells undergo stochastic oscillations in plasma membrane potential (Δψp) leading to associated fluctuations in cytosolic free Ca(2+) concentration ([Ca(2+)]c). Oscillations are not driven by upstream metabolic fluctuations, but rather by autonomous ionic mechanisms, the details of which are unclear. We have investigated the nature of the oscillator, with simultaneous fluorescence monitoring of Δψp, [Ca(2+)]c and exocytosis at single cell resolution, combined with analysis of the occurrence, frequency and amplitude of Δψp oscillations. Oscillations were closely coupled to exocytosis, indicated by coincident synaptopHluorin fluorescence enhancement. L-type Ca(2+) channel inhibitors enhanced Δψp and [Ca(2+)]c oscillation frequency in the presence of pyruvate, but abolished the sustained [Ca(2+)]c response following KCl-depolarization. The L-type Ca(2+) channel inhibitor isradipine did not inhibit oscillation-linked exocytosis. The T-type Ca(2+) channel inhibitor NNC-55 0396 inhibited Δψp and [Ca(2+)]c oscillations, implying that T-channels trigger oscillations and consequent exocytosis.Since distinct ion channels operate in oscillating and non-oscillating cells, quantitative analysis of Δψp and [Ca(2+)]c oscillations in a β-cell population may help to improve our understanding of the link between metabolism and insulin secretion.

Department/s

  • Diabetes - Molecular Metabolism
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2015

Language

English

Pages

111-122

Publication/Series

Biochemical Journal

Volume

471

Issue

1

Document type

Journal article

Publisher

Portland Press

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Diabetes - Molecular Metabolism

ISBN/ISSN/Other

  • ISSN: 0264-6021