Neurotrophic control of channel properties at neuromuscular synapses of rat muscle

Brenner, Hans Rudolf; Sakmann, Bert

doi:10.1113/jphysiol.1983.sp014617

Cited by 72 publications

(42 citation statements)

References 28 publications

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“…Noise analysis combined with calculations of ACh diffusion and comparison of junctional vs. extrajunctional AChR numbers suggest that fetal AChRs are inserted into the denervated end-plate membrane in inactive muscle. As with the same method, adult junctional channels can be readily resolved at denervated rat end-plates (Brenner & Sakmann, 1983) and at ectopic end-plates formed by TTX-blocked nerves in inactive muscles whose extrajunctional ACh sensitivity is comparable to that of denervated muscles (Cangiano, 1985;Brenner et al 1987), it seems unlikely that a significant population of junctional adult AChRs could have been missed in our experiments. Thus, fetal AChRs must be contained in the denervated end-plate membrane.…”

Section: Discussionmentioning

confidence: 66%

“…R. BRENNER AND W. RUDIN muscle activity. For example, in denervated rat muscle, the number of junctional AChRs (Frank, Gautvik & Sommerschild, 1975), their fast gating properties (Brenner & Sakmann, 1983) and junctional folds (Miledi & Slater, 1969) are maintained for up to 3 weeks or longer in the end-plate membrane. In contrast, AChE can be maintained in denervated muscle only by direct stimulation (L0mo, Massoulie & Vigny, 1985) and indirect evidence suggests that the maintenance of junctional AChR stability may be activity dependent (Cangiano, Fumagalli &L0mo, 1987).…”

Section: Introductionmentioning

confidence: 99%

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On the effect of muscle activity on the end‐plate membrane in denervated mouse muscle.

Brenner¹,

Rudin²

1989

The Journal of Physiology

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SUMMARY1. Mouse soleus muscles were denervated and some of them were chronically stimulated. Sixteen to twenty-one days later, the number of junctional acetylcholine receptors (AChR) and their metabolic stability were examined by measuring binding of 125I-a-bungarotoxin, their gating properties by analysis of acetylcholine-induced current fluctuations and the ultrastructure of the end-plate membrane by electron microscopy.2. In agreement with other studies on inactive muscles, no effect of denervation on junctional AChR number could be resolved. However, some of the fast-gating 'adult' AChR channels had been replaced by slowly gating fetal AChRs, their half-life was lowered to 38 h and the folding of the end-plate membrane was reduced.3. These changes were prevented in denervated but stimulated active muscles: the junctional AChR population remained homogenously 'adult', the half-life of junctional AChRs was 13 days and folding of the end-plate membrane remained comparable to that in control muscles.4. The significance of these results is discussed with respect to the role of muscle activity in end-plate development.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

On the effect of muscle activity on the end‐plate membrane in denervated mouse muscle.

Brenner¹,

Rudin²

1989

The Journal of Physiology

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“…In our previous study (Brenner & Sakmann, 1983) channels were found to be exclusively slow up to at least the 7th day of post-soleus-denervation time. However, for easy accessibility end-plates had been selected at the edge of the fibular nerve growth zone.…”

Section: Resultsmentioning

confidence: 72%

“…within the first 6-15 s of the beginning ofACh ejection, were used. With longer application, ACh spreading beyond the end-plate area might activate slowly gating ACh receptor channels in the extrajunctional membrane which would obscure a small population of fast end-plate channels (see Brenner & Sakmann, 1983). Fitting the a.c.f.s by eye showed that in the seven plots with the smallest scatter a fast component of more than 20 % of the total a.c.f.…”

Section: Resultsmentioning

confidence: 99%

“…Such end-plates are formed de novo by a foreign motor nerve transplanted onto the extrajunctional membrane of denervated muscle fibres. They develop within 2-3 weeks along a pattern similar to the one at normal end-plates, with a nerve-induced accumulation of ACh receptors at the site of neuromuscular contact (L0mo & Slater, 1980a) followed by their metabolic stabilization (Reiness & Weinberg, 1981), the deposition of acetylcholinesterase (L0mo & Slater, 1980b) and ending with channel conversion and the formation of junctional folds (Brenner & Sakmann, 1983;Korneliussen & Sommerschild, 1976). We found that, in rat muscle, activity does promote the appearance of the adult channel type at maturing end-plates even if neural influences are eliminated by denervation at an early stage of end-plate development.…”

Section: Introductionmentioning

confidence: 97%

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Control of end‐plate channel properties by neurotrophic effects and by muscle activity in rat.

Brenner

Lømo

Williamson

1987

The Journal of Physiology

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SUMMARY1. The formation of ectopic neuromuscular synapses was induced in rat soleus muscle by implantation of the fibular nerve into the proximal part of the muscle and subsequent sectioning of the soleus nerve. The gating properties of acetylcholine (ACh) receptors at the newly formed end-plates were examined by analysis of acetylcholine-induced membrane current fluctuations.2. In agreement with earlier studies, the apparent mean open time of end-plate channels decreased during synaptic development from about 4 ms to about 1 ms (-60 mV membrane potential, 22°C) within 7-18 days after the soleus nerve had been cut.3. When the fibular nerve was cut at an early stage of end-plate development, fast-gating channels with apparent mean open times of 1 ms characteristic of mature end-plates did not develop within the next 10-14 days.4. When the fibular nerve was cut at an early stage of end-plate development and the soleus muscle was then stimulated chronically via implanted electrodes, fastgating channels did develop in the absence of the nerve terminals within 4-6 days.5. When impulse conduction in the transplanted fibular nerve was blocked chronically at the time of soleus nerve section such that ectopic end-plates formed in inactive muscle, fast-gating channels developed within 12-14 days.6. The results show that motoneurones control the conversion from slow-gating fetal to fast-gating adult-type ACh receptor channels at ectopic end-plates in rat soleus muscles. The conversion occurs in the absence of impulse activity provided the nerve continues to be present. However, it also occurs in the absence of the nerve provided the muscle is active and had received an early priming influence from the nerve. Thus, nerve-evoked muscle activity and nerve-released trophic influences complement each other in controlling the gating properties ofjunctional ACh receptor channels.

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A single gene codes for the nicotinic acetylcholine receptor alpha-subunit in Torpedo marmorata: structural and developmental implications.

Klarsfeld¹,

Devillers‐Thiéry²,

Giraudat³

et al. 1984

The EMBO Journal

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We have used Southern blot hybridization to analyze the genomic structure encoding the alpha‐subunit of the acetylcholine receptor (AChR) in Torpedo marmorata, with cDNA probes isolated from the electric organ. Four different radiolabelled probes, corresponding to various parts of the alpha‐subunit mRNA, hybridized to several genomic fragments of T. marmorata DNA generated by digestion with the restriction enzymes SstI, PvuII and PstI. The same hybridization pattern was observed after washing the blots under low‐ or high‐stringency conditions. As a check for detection sensitivity of heterologous sequences, the same probes were hybridized to PvuII‐digested chicken DNA, revealing bands at low stringency which disappeared at higher stringencies. Unambiguously, two of our probes (one of them entirely within the coding region) hybridized to a single genomic fragment from T. marmorata DNA. This feature, as well as the results of an extensive study of the whole hybridization pattern, points towards the uniqueness of alpha‐subunit‐specific sequences in the genome of T. marmorata. Since overall more bands were found than expected from the cDNA sequence, this alpha‐subunit gene must be split by several introns (at least four, possibly more). The length of this gene is at least 20 kb. The existence of a single alpha‐subunit gene is consistent with the absence of chemical heterogeneity in the NH2‐terminal sequence of the purified alpha‐chain, and supports the view that the two alpha‐chains belonging to one AChR oligomer have an identical primary structure. It also suggests that localization and stabilization of the AChR in well‐defined post‐synaptic areas of T. marmorata electric organ basically relies, during development, on ‘epigenetic’ mechanisms.

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Neurotrophic control of channel properties at neuromuscular synapses of rat muscle

Cited by 72 publications

References 28 publications

On the effect of muscle activity on the end‐plate membrane in denervated mouse muscle.

On the effect of muscle activity on the end‐plate membrane in denervated mouse muscle.

Control of end‐plate channel properties by neurotrophic effects and by muscle activity in rat.

A single gene codes for the nicotinic acetylcholine receptor alpha-subunit in Torpedo marmorata: structural and developmental implications.

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