Total ganglioside ablation at mouse motor nerve terminals alters neurotransmitter release level.
Neuronal membrane gangliosides, forming a large family of sialylated glycosphingolipids, have been hypothesized to play important roles in synaptic transmission. We studied the ex vivo electrophysiological function of neuromuscular junctions of GM2/GD2-synthase*GD3-synthase compound null-mutant mice after acute removal of GM3, the only remaining ganglioside in this mouse, by in vitro treatment with neuraminidase. We found 16% enhancement of the acetylcholine release per nerve impulse at low-rate (0.3 Hz) nerve stimulation. Conversely, the treatment reduced the acetylcholine release evoked by high-rate (40 Hz) nerve stimulation. Also, 25 ms paired-pulse facilitation of endplate potentials was reduced by the neuraminidase-treatment. These effects may indicate a modest modulatory influence of the negative electrical charges carried by the sialic acid molecules of gangliosides on the function of presynaptic Ca(v)2.1 channels, affecting the magnitude and kinetics of the Ca(2+) influx that induces neurotransmitter release from the motor nerve terminal. Our results show that gangliosides are to some extent involved in neurotransmission at the neuromuscular junction, but that their presence is not an absolute requirement in this process.
Zitman
Femke M P
FM
Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
Todorov
Boyan
B
Furukawa
Keiko
K
Furukawa
Koichi
K
Willison
Hugh J
HJ
Plomp
Jaap J
JJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods; D005732:Gangliosides / Q000172:deficiency* / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009439:Neuraminidase / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics
D005732:Gangliosides; D009439:Neuraminidase; D000109:Acetylcholine; D002118:Calcium