Distribution of Na+ channels and ankyrin in neuromuscular junctions is complementary to that of acetylcholine receptors and the 43 kd protein

Flucher, Bernhard E.; Daniels, Mathew P.

doi:10.1016/0896-6273(89)90029-9

Cited by 270 publications

(200 citation statements)

References 54 publications

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“…They also are anchored to the cytoskeleton by an apparently distinct mechanism involving ankyrin (Srinivasan, 1988;Flucher and Daniels, 1989). In the present experiments with ectopic cAgrin 7A4B8 , aggregates of voltage-gated Na ϩ channels were not always colocalized closely with AChR clusters, but they were observed exclusively at or near agrin-induced AChR aggregates.…”

Section: Accumulation Of Na ؉ Channels and The Formation Of Ectopic Jmentioning

confidence: 57%

“…At the normal neuromuscular synapse, Na ϩ channels are located in the depth of the secondary synaptic folds (Flucher and Daniels, 1989), i.e., spatially separate from the AChR clusters, utrophin, and rapsyn (Bewick et al, 1992), which are localized at the crests of folds. They also are anchored to the cytoskeleton by an apparently distinct mechanism involving ankyrin (Srinivasan, 1988;Flucher and Daniels, 1989).…”

Section: Accumulation Of Na ؉ Channels and The Formation Of Ectopic Jmentioning

confidence: 99%

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Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Meier¹,

et al. 1997

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Neural agrin, in the absence of a nerve terminal, can induce the activity-resistant expression of acetylcholine receptor (AChR) subunit genes and the clustering of synapse-specific adult-type AChR channels in nonsynaptic regions of adult skeletal muscle fibers. Here we show that, when expression plasmids for neural agrin are injected into the extrasynaptic region of innervated muscle fibers, the following components of the postsynaptic apparatus are aggregated and colocalized with ectopic agrininduced AChR clusters: laminin-␤2, MuSK, phosphotyrosinecontaining proteins, ␤-dystroglycan, utrophin, and rapsyn. These components have been implicated to play a role in the differentiation of neuromuscular junctions. Furthermore, ErbB2 and ErbB3, which are thought to be involved in the regulation of neurally induced AChR subunit gene expression, were colocalized with agrin-induced AChR aggregates at ectopic nerve-free sites. The postsynaptic muscle membrane also contained a high concentration of voltage-gated Na ϩ channels as well as deep, basal lamina-containing invaginations comparable to the secondary synaptic folds of normal endplates. The ability to induce AChR aggregation in vivo was not observed in experiments with a muscle-specific agrin isoform. Thus, a motor neuron-specific agrin isoform is sufficient to induce a full ectopic postsynaptic apparatus in muscle fibers kept electrically active at their original endplate sites.

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Section: Accumulation Of Na ؉ Channels and The Formation Of Ectopic Jmentioning

confidence: 57%

Section: Accumulation Of Na ؉ Channels and The Formation Of Ectopic Jmentioning

confidence: 99%

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Meier¹,

et al. 1997

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“…AnkyrinG is present in the membrane skeleton of adult rat muscle fibers and is substantially increased at the adult NMJ (Flucher and Daniels, 1989;Kordeli et al, 1998;. During the perinatal period, the pattern of ankyrinG labeling was strikingly similar to that of Na V 1.…”

Section: Ankyring Accumulation At Developing Nmjs Parallels That Of Nmentioning

confidence: 90%

“…AChRs and Na V 1 are segregated in the absence of postsynaptic folds at chicken NMJs The region of high Na V 1 density is closely associated with the postsynaptic folds at mature NMJs (Haimovich et al, 1987;Flucher and Daniels, 1989;. This might indicate that the process that generates the distinct postsynaptic domains occupied by AChRs and Na V 1 is closely associated with the formation of the folds.…”

Section: Syntrophin Is Concentrated At Sites Of High Achr Density Fromentioning

confidence: 92%

“…Acetylcholine receptors (AChRs), concentrated at the crest of the postsynaptic folds (Fertuck and Salpeter, 1974), generate an initial local depolarization in response to transmitter released from the nerve. Voltage-gated sodium channels (Na V 1 channels) (Goldin et al, 2000), concentrated in the depths of the folds and in the perijunctional membrane (Haimovich et al, 1987;Flucher and Daniels, 1989;, convert this local depolarization into a propagating action potential (Martin, 1994). The juxtaposition of these distinct ion channel domains plays an important part in ensuring the effectiveness of neuromuscular transmission (Wood and Slater, 2001), but how they are generated and how the segregation of ion channels is maintained is not understood.…”

Section: Introductionmentioning

confidence: 99%

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Voltage-Gated Sodium Channels and AnkyrinG Occupy a Different Postsynaptic Domain from Acetylcholine Receptors from an Early Stage of Neuromuscular Junction Maturation in Rats

et al. 2003

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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 (Na V 1s) 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 Na V 1 clustering at NMJs. When Na V 1s can first be detected, at birth, they already occupy a postsynaptic domain that is distinct from that occupied by AChRs. At this time, Na V 1s are expressed only in a diffuse area that extends 50 -100 m from the immature NMJ. However, in the region of the high-density AChR cluster at NMJ itself, Na V 1s are actually present in lower density than in the immediately surrounding membrane. These distinctive features of the Na V 1 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 Na V 1s from AChRs. Both Na V 1 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 Na V 1 or ankyrinG. Therefore, syntrophin is unlikely to play an important part in the initial accumulation of Na V 1 at the NMJ. These findings suggest that the segregation of Na V 1 from AChRs begins early in NMJ formation and occurs as a result of the physical exclusion of Na V 1 and ankyrinG from the region of nerve-muscle contact rather than by a process of active clustering.

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Activity-related features of synapse morphology: A study of endbulbs of Held

Ryugo

Pongstaporn

1996

J. Comp. Neurol.

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The myelinated fibers of the auditory nerve can be divided into two separate populations on the basis of sensitivity to sound, average levels of spike activity, and central branching patterns. The synaptic endings of these populations were investigated for the presence of structural specializations that might correlate with levels of neural activity. We applied intracellular recording and staining methods in cats to analyze directly the relationship between spike activity and the structure of synapses using endbulbs of Held, the large synaptic endings in the anteroventral cochlear nucleus. Endbulbs from fibers having low or high levels of activity were examined and compared using light and electron microscopic methods. All endbulbs exhibited relatively large but incomplete coverage by one-to-several lamellae of glial processes. Endbulbs of high activity fibers were large and contained larger mitochondria than endbulbs of low activity fibers. Furthermore, the synapses of high activity endbulbs were on average smaller but more numerous, possessed greater numbers of associated synaptic vesicles, and exhibited greater curvature of their postsynaptic densities. These structural features are hypothesized to reflect specializations that optimize synaptic transmission.

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Distribution of Na+ channels and ankyrin in neuromuscular junctions is complementary to that of acetylcholine receptors and the 43 kd protein

Cited by 270 publications

References 54 publications

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Neural Agrin Induces Ectopic Postsynaptic Specializations in Innervated Muscle Fibers

Voltage-Gated Sodium Channels and AnkyrinG Occupy a Different Postsynaptic Domain from Acetylcholine Receptors from an Early Stage of Neuromuscular Junction Maturation in Rats

Activity-related features of synapse morphology: A study of endbulbs of Held

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