Synapse-glia interactions at the mammalian neuromuscular junction.
Perisynaptic Schwann cells (PSCs) play critical roles in regulating and stabilizing nerve terminals at the mammalian neuromuscular junction (NMJ). However, although these functions are likely regulated by the synaptic properties, the interactions of PSCs with the synaptic elements are not known. Therefore, our goal was to study the interactions between mammalian PSCs in situ and the presynaptic terminals using changes in intracellular Ca(2+) as an indicator of cell activity. Motor nerve stimulation induced an increase in intracellular Ca(2+) in PSCs, and this increase was greatly reduced when transmitter release was blocked. Furthermore, local application of acetylcholine induced Ca(2+) responses that were blocked by the muscarinic antagonist atropine and mimicked by the muscarinic agonist muscarine. The nicotinic antagonist alpha-bungarotoxin had no effect on Ca(2+) responses induced by acetylcholine. Local application of the cotransmitter ATP induced Ca(2+) responses that were unaffected by the P2 antagonist suramin, whereas local application of adenosine induced Ca(2+) responses that were greatly reduced by the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). However, the presence of the A1 antagonist in the perfusate did not block responses induced by ATP. Ca(2+) responses evoked by stimulation of the motor nerve were reduced in the presence of CPT, whereas atropine almost completely abolished them. Ca(2+) responses were further reduced when both antagonists were present simultaneously. Hence, PSCs at the mammalian NMJ respond to the release of neurotransmitter induced by stimulation of the motor nerve through the activation of muscarinic and adenosine A1 receptors.
Rochon
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Centre de Recherche en Sciences Neurologiques and Département de Physiologie, Université de Montréal, Montréal, Quebec, Canada H3C 3J7.
Rousse
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Robitaille
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R
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D009046:Motor Neurons / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011976:Receptors, Muscarinic / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D058915:Purinergic P1 Receptor Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011976:Receptors, Muscarinic; D018047:Receptors, Purinergic P1; D013498:Suramin; D000255:Adenosine Triphosphate; D000241:Adenosine; D000109:Acetylcholine; D002118:Calcium