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Lookup NU author(s): Mark Stocksley,
Dr Alexandra Buckel,
Emeritus Professor Clarke Slater
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Spatial segregation of membrane proteins is a feature of many excitable cells. In skeletal muscle, clusters of acetylcholine receptors (AChRs) and voltage-gated sodium channels (Nav1s) occupy distinct domains at the neuromuscular junction (NMJ). We used quantitative immunolabeling of developing rat soleus muscles to study the mechanism of ion channel segregation and Nav1 clustering at NMJs. When Nav1s can first be detected, at birth, they already occupy a postsynaptic domain that is distinct from that occupied by AChRs. At this time, Nav1s are expressed only in a diffuse area that extends 50-100 μm from the immature NMJ. However, in the region of the high-density AChR cluster at NMJ itself, Nav1s are actually present in lower density than in the immediately surrounding membrane. These distinctive features of the Nav1 distribution at birth are closely correlated with the distribution of ankyrinG immunolabeling. This suggests that an interaction with ankyrinG plays a role in the initial segregation of Nav1s from AChRs. Both Nav1 and ankyrinG become clustered at the NMJ itself 1-2 weeks after birth, coincident with the formation of postsynaptic folds. Syntrophin immunolabeling codistributes with AChRs and never resembles that for Nav1 or ankyrinG. Therefore, syntrophin is unlikely to play an important part in the initial accumulation of Nav1 at the NMJ. These findings suggest that the segregation of Nav1 from AChRs begins early in NMJ formation and occurs as a result of the physical exclusion of Nav1 and ankyrinG from the region of nerve-muscle contact rather than by a process of active clustering.
Author(s): Bailey SJ, Stocksley MA, Buckel A, Young C, Slater CR
Publication type: Article
Publication status: Published
Journal: Journal of Neuroscience
Print publication date: 15/03/2003
ISSN (print): 0270-6474
ISSN (electronic): 1529-2401
Publisher: Society for Neuroscience
PubMed id: 12657669