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Volume 16, Number 16,
Issue of August 15, 1996
pp. 4914-4922
Copyright ©1996 Society for Neuroscience
The Clustering of Axonal Sodium Channels during Development of
the Peripheral Nervous System
Received Feb. 5, 1996; revised May 16, 1996; accepted May 23, 1996.
Ian Vabnick1,
Sanja D. Novakovi 1,
S. Rock Levinson2,
Melitta Schachner3, and
Peter Shrager1
1 Department of Physiology, University of Rochester,
Rochester, New York 14642, 2 Department of Physiology,
University of Colorado, Denver, Colorado 80262, and
3 Department of Neurobiology, Eidgenössische
Technische Hochschule, Zürich CH 8093, Switzerland
The distribution of Na+ channels in rat
peripheral nerve was measured during development by using
immunofluorescence. Small segments of sciatic nerve from postnatal day
0-13 (P0-P13) pups were labeled with an antibody raised against a
well conserved region of the vertebrate Na+
channel. At day P0 axons contained almost no Na+
channel aggregates. The number of clusters increased dramatically
throughout the first week. In almost all cases
Na+ channels clustered in the vicinity of Schwann
cell processes. At least four classes of aggregates were noted.
Clusters formed singly at Schwann cell edges, in pairs or in broad
regions between neighboring Schwann cells, and in more focal zones at
presumptive nodes. Almost all Na+ channel
aggregates had reached the latter stage by the end of the first week.
Histograms plotting the frequency of occurrence of each cluster type
suggested a sequence of events in node formation involving the
initiation of channel aggregation by Schwann cell processes. The
requirement for Schwann cells during sodium channel clustering was
tested by blocking proliferation of these cells with the antimitotic
agent mitomycin C. Na+ channel clustering was
sharply reduced, whereas node formation was normal at a distal site
along the same nerve. Immunocytochemical detection of myelin-associated
glycoprotein (MAG) indicated that Schwann cells must begin to ensheathe
axons before inducing Na+ channel clustering.
Key words:
myelin;
sodium channel;
axon;
Schwann cell;
glia;
development
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