Neuromuscular synaptic function in mice lacking major subsets of gangliosides

Zitman, F.M.P., Todorov, B., Jacobs, B.C., Verschuuren, J.J., Furukawa, K., Willison, H.J. and Plomp, J.J. (2008) Neuromuscular synaptic function in mice lacking major subsets of gangliosides. Neuroscience, 156(4), pp. 885-897. (doi:10.1016/j.neuroscience.2008.08.034)

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Publisher's URL: http://dx.doi.org/10.1016/j.neuroscience.2008.08.034

Abstract

Gangliosides are a family of sialylated glycosphingolipids enriched in the outer leaflet of neuronal membranes, in particular at synapses. Therefore, they have been hypothesized to play a functional role in synaptic transmission. We have measured in detail the electrophysiological parameters of synaptic transmission at the neuromuscular junction (NMJ) ex vivo of a GD3-synthase knockout mouse, expressing only the O- and a-series gangliosides, as well as of a GM2/GD2-synthase*GD3-synthase double-knockout (dKO) mouse, lacking all gangliosides except GM3. No major synaptic deficits were found in either null-mutant. However, some extra degree of rundown of acetylcholine release at high intensity use was present at the dKO NMJ and a temperature-specific increase in acetylcholine release at 35 °C was observed in GD3-synthase knockout NMJs, compared with wild-type. These results indicate that synaptic transmission at the NMJ is not crucially dependent on the particular presence of most ganglioside family members and remains largely intact in the sole presence of GM3 ganglioside. Rather, presynaptic gangliosides appear to play a modulating role in temperature- and use-dependent fine-tuning of transmitter output.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willison, Professor Hugh
Authors: Zitman, F.M.P., Todorov, B., Jacobs, B.C., Verschuuren, J.J., Furukawa, K., Willison, H.J., and Plomp, J.J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Neuroscience
ISSN:0306-4522
Published Online:23 August 2008
Copyright Holders:Copyright © 2008 Elsevier
First Published:First published in Neuroscience 2008, 156(4):885-897
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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