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Hindrik Mulder

Hindrik Mulder

Principal investigator

Hindrik Mulder

Regulated Exocytosis of GABA-containing Synaptic-like Microvesicles in Pancreatic {beta}-cells.

Author

  • Matthias Braun
  • Anna Wendt
  • Bryndis Birnir
  • Jonas Broman
  • Lena Eliasson
  • Juris Galvanovskis
  • Jesper Gromada
  • Hindrik Mulder
  • Patrik Rorsman

Summary, in English

We have explored whether {gamma}-aminobutyric acid (GABA) is released by regulated exocytosis of GABA-containing synaptic-like microvesicles (SLMVs) in insulin-releasing rat pancreatic ß-cells. To this end, ß-cells were engineered to express GABAA-receptor Cl--channels at high density using adenoviral infection. Electron microscopy indicated that the average diameter of the SLMVs is 90 nm, that every ß-cell contains ~3,500 such vesicles, and that insulin-containing large dense core vesicles exclude GABA. Quantal release of GABA, seen as rapidly activating and deactivating Cl--currents, was observed during membrane depolarizations from -70 mV to voltages beyond -40 mV or when Ca2+ was dialysed into the cell interior. Depolarization-evoked GABA release was suppressed when Ca2+ entry was inhibited using Cd2+. Analysis of the kinetics of GABA release revealed that GABA-containing vesicles can be divided into a readily releasable pool and a reserve pool. Simultaneous measurements of GABA release and cell capacitance indicated that exocytosis of SLMVs contributes ~1% of the capacitance signal. Mathematical analysis of the release events suggests that every SLMV contains 0.36 amol of GABA. We conclude that there are two parallel pathways of exocytosis in pancreatic ß-cells and that release of GABA may accordingly be temporally and spatially separated from insulin secretion. This provides a basis for paracrine GABAergic signaling within the islet.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Neurophysiology
  • Diabetes - Molecular Metabolism

Publishing year

2004

Language

English

Pages

191-204

Publication/Series

Journal of General Physiology

Volume

123

Issue

3

Document type

Journal article

Publisher

Rockefeller Institute for Medical Research

Topic

  • Endocrinology and Diabetes

Keywords

  • GABA
  • GAD65
  • pancreatic islets
  • paracrine communication
  • SLMV

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Neurophysiology
  • Diabetes - Molecular Metabolism

ISBN/ISSN/Other

  • ISSN: 0022-1295