Chapter 2 Reliability of neuromuscular transmission and how it is maintained
Section snippets
An introduction to neuromuscular transmission
An important function of all nervous systems is to control muscle contraction so that movements of the body are appropriate to promote survival. In most species specialized motor neurons convey the signals that represent the neural commands for contraction from the central nervous system to the muscle fibers. These signals are transmitted to the individual muscle fibers at highly differentiated neuromuscular junctions (NMJs). In vertebrates, the process of neuromuscular transmission involves
Introduction to the quantal release of ACh
ACh quanta are released from the motor nerve terminal within 100 μs or so of the arrival of the nerve impulse (Katz 1969, Van der Kloot 1994). The events that allow the conversion of depolarization into secretion are complex. At the normal mammalian NMJ, they result in the release of more than enough ACh to ensure a postsynaptic depolarization that evokes an action potential in the muscle fiber (Wood and Slater, 2001). This section presents an account of the main events in the release process.
Diffusion of ACh in the cleft
The rising phase of the EPC lasts about 0.2 ms. During this time, ACh released from the nerve must diffuse across the synaptic cleft, bind to AChRs, which must then undergo a conformational change (“opening”), and Na+ ions must diffuse into the muscle fiber to generate the EPC. The ACh released from a single vesicle diffuses rapidly in the synaptic cleft, with an estimated diffusion coefficient of 1.4 × 10−6 cm2s−1 (Krnjević and Mitchell, 1960). In 0.2 ms, the mean diffusion distance of an ACh
Safety factor of neuromuscular transmission: definition and measurement
The previous sections have described the two core aspects of neuromuscular transmission: the quantal release of ACh by the nerve impulse and the action of that ACh on the muscle fiber to initiate an action potential. In practice, it is the balance between these two processes that determines whether the neural activation of muscle is successful. Many studies have shown that in a wide variety of conditions more ACh is released by each nerve impulse than is required to excite the muscle fiber. The
Modulation of safety factor during normal use
Why is the safety factor for neuromuscular transmission so high? During natural use of the neuromuscular system, the pattern and amount of activity change over a wide range. The ability of the nerve to release transmitter varies significantly as the frequency of activation changes. In particular, during high frequency activity, the quantal content declines significantly. Most published estimates of quantal content that have been used to estimate safety factor (Table 2.1) were determined at low
Biological aspects of safety factor
The description presented so far of the factors that determine the reliability of neuromuscular transmission has been concerned almost entirely with the mature NMJs of normal adult animals. Further, although some mention has been made of differences between the NMJs of frogs and mammals, little attention has been paid to how NMJs in different species, or even within the same species, might differ. The first part of Section 2.6 will consider how NMJs vary between and within species. While a
Response of the neuromuscular junction to trauma or intoxication
The vertebrate neuromuscular system, including the NMJ, is extremely good at repairing itself and restoring function after many sorts of damage. Several different types of cellular mechanism contribute to this ability and help to ensure that effective and reliable activation of muscle is maintained or re‐established. Thus motor axons regenerate well and can form new presynaptic terminals in a few days. For their part, muscle fibers can regenerate after complete destruction and accept and
Overview
The efficacy and reliability of neuromuscular transmission depend on many factors operating at numerous levels of functional organization. As a result many molecules could be targets of pathogenic processes that might interfere with the reliability of neuromuscular transmission. It is perhaps surprising, therefore, that diseases in the NMJ are rare. For example, myasthenia gravis (MG), the most common disease affecting the NMJ directly, has a prevalence in Western countries of only 10–20/100
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Regulation of Gene expression at the neuromuscular Junction
2020, Neuroscience LettersOverexpression of Dok-7 in skeletal muscle enhances neuromuscular transmission with structural alterations of neuromuscular junctions: Implications in robustness of neuromuscular transmission
2020, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Recordings of spontaneous miniature endplate potentials (MEPPs) revealed that the amplitudes and frequencies of MEPPs were increased by 32% and 68% in Dok-7 Tg mice, respectively, compared with WT mice (Fig. 2A and B). Note that each MEPP represents the endplate potential evoked by spontaneous release of a single quantum of ACh without nerve impulse [19]. We further examined the endplate potentials (EPPs) by stimulating the phrenic nerve and found that quantal content of EPPs (the number of ACh quanta released per nerve impulse; please refer to Ref. [19] for detailed information) was increased by 73% in Dok-7 Tg mice (Fig. 2C).
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2020, Clinical Neurophysiology PracticeCitation Excerpt :Due to the reduced acetylcholinesterase (AChE) activity, the ACh released is more effective. Few weeks after successful reinnervation, the quantal content increases to near normal (Slater, 2008). Fibrillation potentials found in EMG represent the APs of single muscle fibers that fire spontaneously in innervation absence (Willmott et al., 2012, Wu et al., 2014, Rubin, 2019).
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2018, Neurologic ClinicsCitation Excerpt :Na+ channel concentration at the endplate involves agrin, ankryn, and syntrophin.22–27 The postsynaptic membrane area is increased by folding into secondary synaptic clefts or folds (see Figs. 1 and 2A).28–34 AChRs are concentrated at the tops of the secondary synaptic folds closest to the nerve terminal.18,35
Plasticity of the mammalian neuromuscular junction and the response to botulinum toxins
2016, The Curated Reference Collection in Neuroscience and Biobehavioral PsychologyThe functional organization of motor nerve terminals
2015, Progress in Neurobiology