Neuromuscular junction motor nerve stimulation

Loewi s work was confined to the autonomic nervous system. Kibjakow (63) and later Dale and his associates tried to extend this concept and suggested that acetylcholine might be the transmitter across ganglionic synapses and at neuromuscular junctions. Their evidence was based essentially on the same type of experiments as was applied in the case of the peripheral autonomic system liberation of acetylcholine after stimulation of preganglionic fibers or motor nerves, stimulation of the sympathetic ganglion and the striated muscle by injection ofij small amounts of ACh, and potentiation of the effects of nerve stimulation by eserinization. The results have been reviewed by Brown (16). 

Measuring muscle-evoked responses to repetitive motor nerve electrical stimulation permits detection of presyn-aptic neuromuscular junction dysfunction. In botulism and the Lambert-Eaton syndrome, repetitive stimulation elicits a smaller than normal skeletal muscle response at the beginning of the stimulus train, due to impaired initial release of acetylcholine-containing vesicles from presyn-aptic terminals of motor neurons followed by a normal or accentuated incremental muscle response during repeated stimulation. This incremental response to repetitive stimulation in presynaptic neuromuscular disorders can be distinguished from the decremental response that characterizes autoimmune myasthenia gravis, which affects the postsynaptic component of neuromuscular junctions. 

Botulinum exotoxin impedes release of neurotransmitter vesicles from cholinergic terminals at neuromuscular junctions. Botulinum exotoxin is ingested with food or, in infants, synthesized in situ by anaerobic bacteria that colonize the gut. A characteristic feature of botulinum paralysis is that the maximal force of muscle contraction increases when motor nerve electrical stimulation is repeated at low frequency, a phenomenon attributable to the recruitment of additional cholinergic vesicles with repetitive depolarization of neuromuscular presynaptic terminals. Local administration of Clostridium botulinum exotoxin is now in vogue for its cosmetic effects and is used for relief of spasticity in dystonia and cerebral palsy [21]. 

Skeletal muscle twitching is due to effects at the skeletal neuromuscular junction, which is innervated by the somatic nervous system, via motor nerves. The anticholinesterase prolongs and intensifies the actions of released acetylcholine at the junction, causing fasciculation (strong, jerky contractions) of skeletal muscle. Normally at the skeletal neuromuscular junction, the released acetylcholine is rapidly hydrolysed by cholinesterases to choline and acetate. This allows repolarization of the muscle membrane to occur following initial stimulation. In the presence of anticholinesterases the acetylcholine remains at the junction for a very prolonged period and produces repeated twitching of the muscle fibres via nicotinic receptors. 

The answer is e. (Murray, pp 505-626. Scriver, pp 4029-4240. Sack, pp 121-138. Wilson, pp 287-320.) The major problem in myasthenia gravis is a marked reduction of acetylcholine receptors on the motor endplate where cranial nerves form a neuromuscular junction with muscles. In these patients, autoantibodies against the acetylcholine receptors effectively reduce receptor numbers. Normally, acetylcholine molecules released by the nerve terminal bind to receptors on the muscle endplate, resulting in a stimulation of contraction by depolarizing the muscle membrane. The condition is improved with drugs that inhibit acetylcholinesterase. 

PHARMACOLOGY, TOXICOLOGY, AND DISPOSITION The reactivating action of oximes in vivo is most marked at the skeletal neuromuscular junction. Following a dose of an organophosphorus compound that produces total blockade of transmission, the intravenous injection of an oxime restores responsiveness of the motor nerve to stimulation within minutes. Antidotal effects are less striking at autonomic effector sites, and the quaternary ammonium group restricts entry into the CNS. 

Neuromuscular Stimulation. Based on a method that has remained unchanged for decades, electrodes are placed within the excitable tissue that provide current to activate certain pathways. This supplements or replaces lost motor or autonomic functions in patients with paralysis. An example is application of electrical pulses to peripheral motor nerves in patients with spinal cord injuries. These pulses lead to action potentials that propagate across neuromuscular junctions and lead to muscle contraction. Coordinating the elicited muscle contractions ultimately reconstitutes function. 

Studies Creatine kinase (CK) was slightly elevated (380 lU/L upper normal for men is 370 lU/L). Liver-function tests and other blood chemistries were normal. The serum anti-neuronal/anti-Hu antibody test was positive. Immunofixation showed a monoclonal IgG-kappa band. Sensory and motor nerve conduction velocities were slightly slowed (dysschwannian) in the lower limbs, and BMG was normal. Cerebrospinal fluid (CSF) protein was slightly elevated (48mg/dL upper normal is 45mg/dL), without detectable lymphocytes or tumor cells. Repetitive neuromuscular junction stimulation at low and high frequency was normal. 

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