Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

ludc web

Anna Wendt

Assistant researcher

ludc web

Corelease and differential exit via the fusion pore of GABA, serotonin, and ATP from LDCV in rat pancreatic beta cells

Author

  • Matthias Braun
  • Anna Wendt
  • Jovita Karanauskaite
  • Juris Galvanovskis
  • Anne Clark
  • Patrick MacDonald
  • Patrik Rorsman

Summary, in English

The release gamma-aminobutyric acid (GABA) and ATP from rat beta cells was monitored using an electrophysiological assay based on overexpression GABAA or P2X2 receptor ion channels. Exocytosis of LDCVs, detected by carbon fiber amperometry of serotonin, correlated strongly (similar to 80%) with ATP release. The increase in membrane capacitance per ATP release event was 3.4 fF, close to the expected capacitance of an individual LDCV with a diameter of 0.3 mu m. ATP and GABA were coreleased with serotonin with the same probability. Immunogold electron microscopy revealed that similar to 15% of the LDCVs contain GABA. Prespike "pedestals," reflecting exit of granule constituents via the fusion pore, were less frequently observed for ATP than for serotonin or GABA and the relative amplitude (amplitude of foot compared to spike) was smaller: in some cases the ATP-dependent pedestal was missing entirely. An inward tonic current, not dependent on glucose and inhibited by the GABAA receptor antagonist SR95531, was observed in beta cells in clusters of islet cells. Noise analysis indicated that it was due to the activity of individual channels with a conductance of 30 pS, the same as expected for individual GABA(A) Cl- channels with the ionic gradients used. We conclude that (a) LDCVs accumulate ATP and serotonin; (b) regulated release of GABA can be accounted for by exocytosis of a subset of insulin-containing LDCVs; (c) the fusion pore of LDCVs exhibits selectivity and compounds are differentially released depending on their chemical properties (including size); and (d) a glucose-independent nonvesicular form of GABA release exists in beta cells.

Department/s

  • Islet cell physiology
  • Diabetes - Islet Cell Exocytosis
  • Department of Experimental Medical Science

Publishing year

2007

Language

English

Pages

221-231

Publication/Series

Journal of General Physiology

Volume

129

Issue

3

Document type

Journal article

Publisher

Rockefeller Institute for Medical Research

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Islet cell physiology
  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 0022-1295