Overview of neuromuscular junction toxins
- Tracy Weimer, MD
Tracy Weimer, MD
- Assistant Professor, Department of Neurology
- West Virginia University School of Medicine
- Laurie Gutmann, MD
Laurie Gutmann, MD
- Professor and Vice Chair of Clinical Research
- University of Iowa
Signal transduction at the neuromuscular junction is a multistep, complex process required for many of the functions that sustain life. Neuromuscular toxins act in various ways to inhibit this process. These toxins are naturally occurring , and some have been developed as biochemical weapons.
This topic will briefly discuss the neuromuscular transmission disorders due to botulism, tick paralysis, snake venom, organophosphates and carbamates, and hypermagnesemia or hypocalcemia.
Acquired myasthenia gravis, congenital and neonatal myasthenia gravis, and Lambert-Eaton myasthenic syndrome are discussed separately. (See "Pathogenesis of myasthenia gravis" and "Clinical manifestations of myasthenia gravis" and "Neuromuscular junction disorders in newborns and infants" and "Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome".)
THE NEUROMUSCULAR JUNCTION
The neuromuscular junction consists of a presynaptic axon terminal and a postsynaptic muscle end plate (figure 1). Within the presynaptic terminal are vesicles containing acetylcholine, adenosine triphosphate (ATP), magnesium, and calcium [2,3]. Most of these vesicles are bound to the actin cytoskeleton by proteins called synapsins. When an action potential induces opening of calcium channels, increased intracellular calcium levels promote phosphorylation of synapsins. This phosphorylation results in release of the vesicles from their cytoskeletal sites .
After release from the cytoskeleton, vesicles become bound at the presynaptic membrane terminal in areas called active zones [2,5]. This "docking" allows rapid exocytosis of the vesicles. Docking is mediated by proteins termed SNARES (soluble N-ethylmaleimide-sensitive-fusion-attachment protein receptors). SNARES attached to the terminal membrane (t-SNARES) form complexes with proteins located on the vesicle (v-SNARES) [6-8].
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- THE NEUROMUSCULAR JUNCTION
- Clinical features
- TICK PARALYSIS
- Clinical features
- SNAKE VENOM
- Clinical features and diagnosis
- Clinical features and diagnosis
- ORGANOPHOSPHATE AND CARBAMATE TOXICITY
- Clinical features
- SUMMARY AND RECOMMENDATIONS