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)

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 > School of Infection & Immunity
• 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