The acetylcholine channel open time in chick muscle is not decreased following innervation.

Schuetze, SM

doi:10.1113/jphysiol.1980.sp013274

Cited by 56 publications

(35 citation statements)

References 32 publications

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“…Miniature endplate currents (MEPCs) and AcCho-induced current fluctuations were recorded extracellularly as described (8,9), except that in each case the electrode was connected to a List LM EPC-5 patch-clamp amplifier rather than to a voltage amplifier. MEPCs or noise records were obtained from the same endplates before and after the preparation was incubated with Ab or control IgG.…”

Section: Methodsmentioning

confidence: 99%

Myasthenic serum selectively blocks acetylcholine receptors with long channel open times at developing rat endplates.

Schuetze¹,

Vicini²,

Hall³

1985

Proc. Natl. Acad. Sci. U.S.A.

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We have examined the physiological effects of antibodies from a highly specific myasthenic serum on acetylcholine receptors at developing rat endplates. The antibodies reduced the amplitude of miniature endplate potentials by 60% in 3-to 6-day-old animals but had no effect after day 14. Between days 7 and 12 the antibodies had an intermediate effect. This is the same period during which acetylcholine receptors with long channel open times (slow channels) disappear and receptors with short open times (fast channels) increase in number. Therefore, we examined the effect of the antibodies at endplates with a mixture of channel types more carefully. At all times tested, both noise analysis and analysis of miniature endplate currents showed that the antibodies reduced slow channel activity selectively. Single-channel recordings indicated that acetylcholine receptors that remained active after antibody treatment had normal gating properties. Thus, the antibodies appeared to silence slow channels selectively.Acetylcholine receptors (AcChoRs) change in several ways during formation of the skeletal neuromuscular junction (reviewed in ref. 1). At developing rat endplates, a striking functional change occurs postnatally: the apparent mean channel open time decreases by a factor of 3-5, and the single-channel conductance increases by about 50%. In rat soleus (20) and diaphragm (3) muscles, these changes in gating properties occur over a 2-week period beginning several days after birth. The transition at any individual endplate probably occurs within a few days (3, 4). During the transition, individual endplates contain a mixture of slow, embryonic-like channels and fast, adult-like channels.Several molecular properties of the AcChoR also change during muscle endplate development (reviewed in ref. 1). One of the molecular changes is detected by a class of antibodies (Abs) found in the serum of most patients with myasthenia gravis. These Abs recognize one or more determinants that are present on AcChoRs in the extrajunctional membrane of embryonic muscle but are not found on AcChoRs at adult endplates (5). Recently, a myasthenic serum that is highly specific for the embryonic type of AcChoR has been used to characterize AcChoRs at developing endplates (6). AcChoRs at endplates of newborn, but not adult, rats bind Abs in this serum. Endplate AcChoRs lose their reactivity to the Abs during the second and third postnatal weeks (7).The parallel in time course of the loss of immunoreactivity and the transition in channel properties suggests that Abs in this serum might bind specifically to AcChoRs with slow, embryonic-like channels. Because these Abs block AcChoR function (21), we have been able to test this hypothesis explicitly by examining the physiological effects of the myasthenic serum at developing endplates that contain a mixture of channel types. We report here that at all times tested, the serum appeared to block the slow channels selectively. This suggests that Abs in this serum detect a structural change in the...

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Section: Methodsmentioning

confidence: 99%

Myasthenic serum selectively blocks acetylcholine receptors with long channel open times at developing rat endplates.

Schuetze¹,

Vicini²,

Hall³

1985

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, in embryonic amphibian muscle, the frequency of fast channel openings increases with age even when the cultures are raised in the absence of neurones (Brehm et al 1982(Brehm et al , 1984, suggesting that an innervating nerve may simply concentrate preformed adult-type ACh receptors underneath its terminals. In chicken muscle, on the other hand, channel conversion does not occur even at normally innervated end-plates (Schuetze, 1980). Channel conversion at eleven of twenty-three denervated end-plates in chronically stimulated muscle was incomplete.…”

Section: Fast Adult-type Channels Develop At Denervated End-plates Inmentioning

confidence: 95%

“…While in rat muscle sustained activity seems to promote channel conversion (Brenner, Meier & Widmer, 1983;Brenner, 1984), muscle paralysis during end-plate formation in amphibia leaves the development of adult channels unaffected (Kullberg, Owens & Vickers, 1985), and fast adult channels develop even in amphibian aneural muscle cultures (Brehm, Kidokoro & MoodyCorbett, 1984;Brehm, Steinbach & Kidokoro, 1982). At avian end-plates, on the other hand, channel conversion is not observed at all (Schuetze, 1980). These findings suggest that the development of adult channels may be regulated differently in different species and, hence, they may not be compared.…”

Section: Introductionmentioning

confidence: 99%

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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“…The effect is selective in that no change in 6-or y-subunit mRNA was detected. In chick muscle, although y-subunit mRNA is not detectable in mature innervated muscle (11), no E-subunit gene has been reported, and no change in channel conductance or open time occurs during development in vitro or in vivo (21). Therefore, we have studied the effect of ARIA on the level of s-subunit mRNA in mouse myotubes.…”

mentioning

confidence: 99%

Acetylcholine receptor-inducing activity stimulates expression of the epsilon-subunit gene of the muscle acetylcholine receptor.

Martinou

Falls

Fischbach

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

133

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Motor neurons regulate the transcription of acetylcholine receptor subunit genes in postsynaptic muscle fibers both through muscle electrical activity produced by motor neuron acetylcholine release and by mechanisms independent of such transmitter release. Factors secreted by the motor neuron may mediate activity-independent regulation, including the postnatal switch from aj2fyS (embryonic type) to r2fiES (adult type) receptors. We have investigated the effect of putative trophic factors, agents affecting second-messenger systems, and muscle activity on the levels of acetylcholine receptor subunit mRNAs in primary mouse muscle cultures. We found that ARIA (acetylcholine receptor-inducing activity), a 42-kDa glycoprotein purified on the basis of its ability to increase the synthesis of acetylcholine receptors in chick myotubes, increases E-subunit mRNA levels up to 10-fold. In addition, ARIA stimulated a-, v-, and 6-subunit mRNA levels 2-fold but had no effect on the expression of the 8-subunit gene. These effects of ARIA were independent ofmuscle activity, and they were not mimicked by calcitonin gene-related peptide nor by thyroxine, forskolin, phorbol 12-myristate 13-acetate, the calcium ionophore A23187, basic fibroblast growth factor, or transforming growth factor B. Based on these data, we suggest that ARIA may act at the mammalian neuromuscular junction to induce adult-type acetylcholine receptors.

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The acetylcholine channel open time in chick muscle is not decreased following innervation.

Cited by 56 publications

References 32 publications

Myasthenic serum selectively blocks acetylcholine receptors with long channel open times at developing rat endplates.

Myasthenic serum selectively blocks acetylcholine receptors with long channel open times at developing rat endplates.

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

Acetylcholine receptor-inducing activity stimulates expression of the epsilon-subunit gene of the muscle acetylcholine receptor.

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