Two Populations of AChR in Rat Myotubes Have Different Degradation Rates and Responses to cAMP

O'Malley, James P.; Rubin, Lee L.; Salpeter, Miriam M.

doi:10.1006/excr.1993.1220

Cited by 12 publications

(27 citation statements)

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“…Figure 4 shows that 500 M dB-cAM P was able to stabilize the accelerated Rs receptors in md x muscles, as shown previously for normal muscles (Shyng et al, 1991;Xu and Salpeter, 1995). In addition, as seen previously in cultures from albino rats (O'Malley et al, 1993), dB-cAM P was able to stabilize the Rs receptors (ϳ10% of total population) on md x muscles in cell culture (Fig. 5A,B) without affecting the R r population.…”

Section: Stabilization Of Rs Achrs By Camp In MDX Musclessupporting

confidence: 87%

“…For that purpose, we used organ culture to study AChRs on long-term (21 d) denervated diaphragms and tissue culture to study the AChRs on aneural myotubes derived from leg muscles. In both systems the AChRs had the two component degradation curves characteristic of AChRs synthesized in noninnervated muscle (Shyng and Salpeter, 1990;O'Malley et al, 1993O'Malley et al, , 1997. We saw no difference between mdx and control muscles in the degradation rates of either the fast component Rr or the small (10%) slow component of accelerated Rs, normally seen in such muscles (Figs.…”

Section: Rr Degradationmentioning

confidence: 65%

“…Leg muscles were excised from decapitated, 4-week old md x and control mice. C ell cultures were prepared according to O'Malley et al (1993O'Malley et al ( , 1996, with minor modifications. Briefly, the muscles were digested in 0.1% collagenase (Sigma) in Kreb's buffer at 37°C for 2-3 hr and plated in DM EM (Life Technologies, Grand Island, N Y) supplemented with penicillin (200 U/ml) and streptomycin (200 g /ml) with 10% FBS (Life Technologies) for 3 d before changing to DM EM f usion medium containing 5% horse serum (Life Technologies) (Dickson et al, 1992).…”

Section: Degradation Of Achr S In Adult Musclesmentioning

confidence: 99%

“…Data were normalized to 100% on day 0 and fitted to two exponentials according to O'Malley et al (1993).…”

Section: Degradation Of Achr S In Adult Musclesmentioning

confidence: 99%

“…Eventually, however, Rr are downregulated by innervation (Fumagalli et al, 1990;Andreose et al, 1993). The mechanism by which the nerve differentially regulates Rs and Rr degradation is not yet known, but both muscle activity and trophic factors seem to be involved (Avila et al, 1989;Garcia et al, 1990;Shyng et al, 1991;Andreose et al, 1993;O'Malley et al, 1993O'Malley et al, , 1997Xu and Salpeter, 1995).…”

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Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Salpeter

1997

J. Neurosci.

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Acetylcholine receptors (AChRs) are present at the top of the postsynaptic membrane of the neuromuscular junction (NMJ) at very high density, possibly anchored to cytoskeletal elements. The present study investigated whether AChR degradation is affected in animals lacking dystrophin, a protein that is an integral part of the cytoskeletal complex and is missing in Duchenne muscular dystrophy. The animal model for Duchenne muscular dystrophy, the mutant mdx mouse, was used to determine whether disruption of the cytoskeleton, caused by the absence of dystrophin, affects AChR degradation. Of the two populations of junctional AChRs, Rs (expressed in innervated adult muscles) and Rr (expressed in embryonic or denervated muscles), only Rs are affected in mdx animals. In innervated mdx soleus, diaphragm, and sternomastoid muscles, the AChRs have an accelerated degradation rate (t 1/2 of ϳ3-5 d), similar to that acquired by Rs in control muscles after denervation. The Rs in mdx NMJs do not accelerate further when the muscles are denervated. The absence of dystrophin does not affect the degradation rate of the Rr AChRs (t 1/2 of 1 d), which are expressed after denervation in mdx as in control muscles. These results suggest that dystrophin or an intact cytoskeletal complex may be required for neuronal stabilization of Rs receptors at the adult neuromuscular junctions.

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Section: Stabilization Of Rs Achrs By Camp In MDX Musclessupporting

confidence: 87%

Section: Rr Degradationmentioning

confidence: 65%

Section: Degradation Of Achr S In Adult Musclesmentioning

confidence: 99%

“…Data were normalized to 100% on day 0 and fitted to two exponentials according to O'Malley et al (1993).…”

Section: Degradation Of Achr S In Adult Musclesmentioning

confidence: 99%

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confidence: 99%

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Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Salpeter

1997

J. Neurosci.

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Differential influence of electrical blocking agents on embryonic acetylcholine receptor mRNA levels in long‐term cultures of aneural mammalian myotubes

Carlson

Adkins

Blake

et al. 1994

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The influence of spontaneous muscle activity on acetylcholine receptor (AChR) expression was examined by exposing long-term cultures of mammalian myotubes to two pharmacological agents that have similar effects on the rate of spontaneous contractile activity but pharmacologically distinct actions on voltage gated Na+ channels. Previous studies by other investigators have shown that tetrodotoxin upregulates and that veratridine downregulates surface AChR expression in short-term mammalian muscle cultures. In order to determine whether these drugs have disparate actions on AChR mRNA levels, myotubes were exposed to either tetrodotoxin or veratridine for a period of 10 days, and measurements of the relative levels of embryonic AChR subunit mRNAs (alpha, beta, gamma, delta) were obtained during and following the period of drug exposure. Veratridine produced a substantial decrease (between 33% and 50% reduction), while tetrodotoxin produced a relatively small increase (between 17% and 23%), in each of the AChR subunit mRNAs after 6 days of drug exposure. At 23 days in culture, spontaneously active myotubes exhibited a decrease in the relative levels of each of the AChR subunit mRNAs. Myotubes previously exposed to either veratridine or tetrodotoxin exhibited elevated levels of beta, gamma, and delta AChR subunit mRNAs 6 days after cessation of drug treatment, thus suggesting that a period of muscle inactivity can induce sustained influences on some AChR mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)

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Muscle-Specific Agrin Isoforms Reduce Phosphorylation of AChR γ and δ Subunits in Cultured Muscle Cells

Meier

Rüegg

Wallace

1998

Molecular and Cellular Neuroscience

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Two Populations of AChR in Rat Myotubes Have Different Degradation Rates and Responses to cAMP

Cited by 12 publications

References 0 publications

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Acetylcholine Receptors in Innervated Muscles of DystrophicmdxMice Degrade as after Denervation

Differential influence of electrical blocking agents on embryonic acetylcholine receptor mRNA levels in long‐term cultures of aneural mammalian myotubes

Muscle-Specific Agrin Isoforms Reduce Phosphorylation of AChR γ and δ Subunits in Cultured Muscle Cells

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