Biomaterial Database

Studies on neurotrophic regulation of murine skeletal muscle. 1978

D A Mathers, and S Thesleff

1. A quantitative comparison was made of the effects of the paralysis caused by botulinum toxin (BoTx) type A with those of surgical denervation on the development of tetrodotoxin (TTX) resistant action potentials and of extrajunctional acetylcholine (ACh) receptors in rat and mouse skeletal muscle.2. After surgical denervation, TTX resistant action potentials were present in all fibres on the third day and their rate of rise and amount of overshoot reached peak values at the fifth day. BoTx poisoning failed, despite causing complete paralysis, to induce TTX resistant action potentials in all fibres and their average rate of rise was at all times (4-12 days) only about half that in denervated fibres. Similarly BoTx poisoning induced a smaller increase than surgical denervation in the number of extrajunctional ACh receptors, measured as (3)H-labelled Naja naja siamensis alpha-neurotoxin binding sites.3. Surgical denervation of BoTx poisoned muscles induced TTX resistant action potentials in all fibres and their rate of rise and amount of overshoot were 2-3 times those in BoTx poisoned muscles only. Denervation also significantly increased the binding of labelled alpha-neurotoxin. These effects of denervation were prevented by the administration of actinomycin D, a blocker of protein synthesis.4. Administration of the alpha-neurotoxin to BoTx poisoned animals resulted in the appearance of TTX resistant action potentials in all fibres and in a significant increase in their rate of rise and overshoot.5. The results show that, despite causing complete paralysis, BoTx is less effective than surgical denervation in inducing denervatory changes in skeletal muscle. This suggests that the BoTx poisoned nerve has an influence which suppresses the appearance of denervation signs. Since the alpha-neurotoxin blocked this influence remaining release of ACh, quantal or non-quantal, may be responsible for this neurotrophic action.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009121	Muscle Denervation	The resection or removal of the innervation of a muscle or muscle tissue.	Denervation, Muscle,Denervations, Muscle,Muscle Denervations
D009132	Muscles	Contractile tissue that produces movement in animals.	Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D009469	Neuromuscular Junction	The synapse between a neuron and a muscle.	Myoneural Junction,Nerve-Muscle Preparation,Junction, Myoneural,Junction, Neuromuscular,Junctions, Myoneural,Junctions, Neuromuscular,Myoneural Junctions,Nerve Muscle Preparation,Nerve-Muscle Preparations,Neuromuscular Junctions,Preparation, Nerve-Muscle,Preparations, Nerve-Muscle
D011950	Receptors, Cholinergic	Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.	ACh Receptor,Acetylcholine Receptor,Acetylcholine Receptors,Cholinergic Receptor,Cholinergic Receptors,Cholinoceptive Sites,Cholinoceptor,Cholinoceptors,Receptors, Acetylcholine,ACh Receptors,Receptors, ACh,Receptor, ACh,Receptor, Acetylcholine,Receptor, Cholinergic,Sites, Cholinoceptive
D001905	Botulinum Toxins	Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.	Botulin,Botulinum Neurotoxin,Botulinum Neurotoxins,Clostridium botulinum Toxins,Botulinum Toxin,Neurotoxin, Botulinum,Neurotoxins, Botulinum,Toxin, Botulinum,Toxins, Botulinum,Toxins, Clostridium botulinum
D003039	Cobra Neurotoxin Proteins	Toxins, contained in cobra (Naja) venom that block cholinergic receptors; two specific proteins have been described, the small (short, Type I) and the large (long, Type II) which also exist in other Elapid venoms.	Cobra Neurotoxins,Cobrotoxin,Neurotoxin Proteins, Cobra,Neurotoxins, Cobra,Proteins, Cobra Neurotoxin
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013779	Tetrodotoxin	An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.	Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu