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S Heinemann

Publications and source records attributed to S Heinemann.

9 recordsLinked to original sources

Acetylcholine receptor degradation in adult rat diaphragms in organ culture and the effect of anti-acetylcholine receptor antibodies.

Acetylcholine receptor located at the neuromuscular synapse of normal innervated adult muscle fibers is extremely stable metabolically. We have studied the kinetics of receptor degradation in both normal innervated and denervated rat diaphragms in organ culture. These studies show that degradation of receptor-bound 125I-alpha-bungarotoxin is a valid measure of junctional receptor degradation. Degradation of junctional receptor is similar or identical to degradation of extrajunctional receptor in many ways: 1) both require energy, 2) both are inhibited by specific lysosomal protease inhibitors, 3) both are inhibited by treatment with colchicine, and 4) both are stimulated by treatment with anti-acetylcholine receptor antibodies. The one important distinction between degradation of junctional and extrajunctional receptor is a 10-fold difference in rate constant for the process.

Acetylcholine

Degradation of acetylcholine receptor in diaphragms of rats with experimental autoimmune myasthenia gravis.

The degradation of acetylcholine receptor observed in denervated and innervated normal rat diaphragms in organ culture is stimulated by exogenous antireceptor serum. In this paper we demonstrate that diaphragms from rats with experimental autoimmune myasthenia gravis contain reduced amounts of acetylcholine receptor. Acetylcholine receptor from myasthenic, but not from normal, rats has antibody bound to it and is degraded at an accelerated rate. We conclude that in the chronic phase of experimental autoimmune myasthenia gravis increased acetylcholine receptor degradation can be accounted for by a mechanism involving antigenic modulation, and that such a process can contribute to the clinical symptoms of impaired neuromuscular transmission.

Acetylcholine

Degradation of junctional and extrajunctional acetylcholine receptors by developing rat skeletal muscle.

We have examined the rate of degradation of the total acetylcholine receptor content of diaphragm muscles of young rats and have found that even in muscles from 1-day-old rats some receptors are metabolically more stable than adult extrajunctional receptors. Further experiments have shown that acetylcholine receptors at junctional regions from young rats are degraded slowly, whereas those in extrajunctional regions are degraded rapidly. The results demonstrate that junctional acetylcholine receptors in rat diaphragm are degraded at a slow rate characteristic of adult junctional receptors at all ages after birth.

Acetylcholine

Biology of cultured nerve and muscle.

Cells from the nervous system can be grown in culture and exhibit many of the biophysical, biochemical, and morphological properties found in vivo. They can be induced to differentiate in culture and perform some of the interactions that occur in the nervous system, including synaptogenesis. A number of important questions relating to nervous system development and function have been approached in culture in ways that cannot be done in vivo. The use of clonal cell lines should lead to rapid progress in the analysis of the nervous system at the chemical level.

Acetylcholine

Cholinergic metabolism and synapse formation by a rat nerve cell line.

The PC12 clone of a rat pheochromocytoma is able to synthesize acetylcholine. The amount of acetylcholine synthesized, and the specific activity of choline O-acetyltransferase (acetyl-CoA:choline O-acetyltransferase, EC 2.3.1.6), varies as a function of the culture growth curve and is dependent on cell density. The specific activity of choline acetyltransferase is increased by nerve growth factor, growth-conditioned medium from a variety of cell types, and adenosine 3':5'-monophosphate. Finally, the PC12 cell line is able to form cholinergic synapses with a clonal cell line of skeletal muscle origin.

Acetylcholine

Modulation of acetylcholine receptor by antibody against the receptor.

Antibody against acetylcholine receptor induces an increase in the rate of degradation of acetylcholine receptors on a mouse cell line (BC(3)H-1) and cultured rat skeletal muscle. The increased rate of degradation results in a lowered density of acetylcholine receptors on muscle membrane and a lowered sensitivity to iontophoretically applied acetylcholine. The modulation of acetylcholine receptor is energy, temperature, and time dependent and may be related to antigenic modulation found in other systems. Acetylcholine noise analysis demonstrates that antibody against acetylcholine receptor reduces the channel mean conductance and mean open time slightly. It is concluded that antibody binds to the acetylcholine receptor, impairs its function, and induces receptor degradation. This results in a lowered density of acetylcholine receptor and a lowered sensitivity to acetylcholine. Patients with myasthenia gravis have antibodies to their acetylcholine receptor in their serum. Antigenic modulation of receptor in the muscle of patients with myasthenia gravis could contribute to the observed decrease in amplitudes of miniature endplate potentials and in muscle acetylcholine sensitivity, and the symptoms of muscular weakness.

Acetylcholine

Ultrastructural changes accompanying the induced differentiation of clonal rat nerve and glia.

Dibutyryladenosine 3'-5' monophosphate (DBcAMP) induces ultrastructural transformations in clonal rat nerve and glia. Cells cultured in the presence of DBcAMP contain large numbers of aligned microtubules and microfilaments in their elongated processes, while control cultures without DBcAMP are relatively devoid of these structures. In addition, the cells exposed to DBcAMP contain 2000 A to 6000 A vesicles which are not observed in control cells.

Animals