ENTRIES A–Z
Philip Winn in Dictionary of Biological Psychology, 2003
The neuromuscular junction is the point at which a motor neuron (also known as a MOTONEURON; see MOTOR NEURONS) meets a MUSCLE FIBRE: it is a specialized form of SYNAPTIC TERMINAL. It is the point at which neuronal activity is translated into muscular action. Motor neurons have their cell bodies in the ventral horns of the SPINAL CORD, where they receive thousands of different synaptic inputs which may be transformed into ACTION POTENTIAL activity travelling along the AXON (which leaves at the VENTRAL ROOT). Shortly before arrival at a muscle, the axon branches extensively, each branch making contact with a different muscle fibre within the target muscle. The various points of contact are of course the neuromuscular junctions. Arrival of the action potential at these produces (in VERTEBRATES) liberation of the neurotransmitter ACETYLCHOLINE. The DEPOLARIZATION produced by acetylcholine is large and effective enough to generate an action potential in each of the muscle fibres innervated: the depolarization is called the ENDPLATE POTENTIAL. The critical effect of the endplate potential is to permit influx of CALCIUM ions (Ca2+) into a MYOFILAMENT.
The Neuromuscular Junction
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
The endplate voltage, conventionally referred to as the endplate potential (epp), recorded following a nerve AP is the depolarization caused by the epc acting on the parallel combination of resistance and capacitance of the muscle membrane. The general shape of the epp is illustrated in Figure 5.12. The amplitude of the epp is 50–70 mV above a resting membrane voltage of about –90 mV for the muscle. Since the threshold of the muscle AP is 15–25 mV above the resting voltage, a muscle AP is generated well before the epp reaches its peak. Hence, the full time course of the epp can only be recorded with the muscle AP suppressed. The presence of voltage-gated Na+ channels in the depths of the junctional folds serves to reduce the threshold for the muscle AP. The size of the epp rapidly declines with high-frequency repetitive stimulation of 20–40 APs because of a decrease in the number of vesicles released, but levels off thereafter at about 65% of its size for a single AP. As may be expected, this decline in the size of the epp with repetitive stimulation is more marked at the NMJs of fast muscle fibers compared to those of slow muscle fibers (Section 9.3.2).
The neurologic approach
Stanley Berent, James W. Albers in Neurobehavioral Toxicology, 2012
The electrical response to repetitive motor nerve stimulation can be used to evaluate neuromuscular transmission (Ozdemir & Young, 1976). When neuromuscular transmission is impaired, there is a decrement in the motor response at low stimulation rates (3 Hz) (Massey, 1990; Albers & Leonard, 1992). At this stimulation rate, normal subjects show no evidence of a decremental response. Acetylcholine is released from the nerve terminal when the nerve is depolarized. Acetylcholine molecules diffuse across the neuromuscular junction and interact with acetylcholine receptors (AChR) on the muscle membrane. This interaction results in a configurational change in sodium channels, producing an endplate potential. If the endplate potential is sufficiently large, a muscle action potential is generated and the muscle fiber contracts. Factors important to this response include, among other factors, sufficient availability of acetylcholine, appropriate inactivation of acetylcholine in the synaptic cleft, and intact AChR. Abnormality of any of these factors can impair neuromuscular transmission.
Advances in autoimmune myasthenia gravis management
Published in Expert Review of Neurotherapeutics, 2018
Shuhui Wang, Iva Breskovska, Shreya Gandhy, Anna Rostedt Punga, Jeffery T. Guptill, Henry J. Kaminski
Regardless of the autoantibody type, the underlying physiological abnormality leading to skeletal muscle weakness is the reduction of the safety factor for neuromuscular transmission [29,30]. The safety factor is the difference in the endplate potential and the threshold potential required to generate an action potential, which will then trigger contraction of the muscle fiber. Whether there are AChR, MuSK, or no other autoantibody presently detected, the reduction of AChR is the primary contributor to a reduced endplate potential. Loss of synaptic folds and post-synaptic sodium channels serve to reduce the safety factor further. This tenuous situation of low safety factors among neuromuscular junctions across all skeletal muscle in a patient leads to the variability in weakness depending on the level of activity, degree of damage, temperature, and unknown factors produces the characteristic fatigable weakness that patients experience. Repetitive neuronal activity leads to a small reduction in release of acetylcholine, which under normal conditions is unimportant, but at the myasthenic junction can reduce the endplate potential that is required for action potential generation with consequent reduced muscle force generation and weakness. The basal lamina of the synaptic cleft is concentrated with acetylcholinesterase (AChE), which serves to terminate the activity of acetylcholine released from the presynaptic nerve terminal. AChE inhibition increases the available acetylcholine for binding to the AChR, thereby increasing the endplate potential and improving a compromise of the safety factor.
Sensory neurotization of muscle: past, present and future considerations
Published in Journal of Plastic Surgery and Hand Surgery, 2019
Steven D. Kozusko, Alexander J. Kaminsky, Louisa C. Boyd, Petros Konofaos
There are a few contraindications reported for sensory neurotization. If the period of denervation time is substantial then permanent muscle atrophy with loss of end-plate potential precludes efficacy of sensory neurotization. If the muscle has been severely damaged and restoration of neuronal input would have no functional recovery then sensory neurotization is inappropriate. Lastly, if the extremity is severely damaged or there is marked joint stiffness and fibrotic muscles then sensory neurotization would not provide substantial benefit [27].
Review of the mechanism underlying mefloquine-induced neurotoxicity
Published in Critical Reviews in Toxicology, 2021
Airton C. Martins, Monica M. B. Paoliello, Anca O. Docea, Abel Santamaria, Alexey A. Tinkov, Anatoly V. Skalny, Michael Aschner
The proposed role of altered Ca2+ homeostasis in mefloquine-induced neurotoxicity, and its relationship to other pathogenetic mechanisms are shown in Figure 2. Mefloquine has been found to be a noncompetitive inhibitor of both acetylcholinesterase (AChE, located in neural synapses), and butyrylcholinesterase (BChE, located in the liver and blood) (Lim and Go 1985). Inhibition of AChE alters both peripheral and central cholinergic synaptic transmission. AChE catalyzes the hydrolysis of acetylcholine to acetate and choline to clear acetylcholine from the cholinergic synapse, attenuating neurotransmission. Inhibition of acetylcholinesterase by mefloquine prolongs the stimulation of muscarinic or nicotinic acetylcholine receptors, disrupting neurotransmission. Indeed, mefloquine significantly increases mean miniature endplate potential (MEPP) frequency, increases MEPP amplitude, and prolongs its duration at the neuromuscular junction at minimum mefloquine concentration of 10 μM (McArdle et al. 2005, 2006), suggesting that mefloquine may contribute to neurotoxicity through altered cholinergic synaptic transmission. The prolonged neurotransmission by acetylcholine may be responsible for the disruption of calcium (Ca2+) homeostasis, resulting in neurotoxic effects. Acetylcholine binds and interacts with nicotinic (nAChR) and muscarinic acetylcholine receptors (mAChR), which results in increased intracellular Ca2+concentrations. nAChRs are ionotropic receptors that bind acetylcholine and are permeable to sodium, potassium, and Ca2+ (Siegel et al. 1999) (Figure 2). mAChRs bind acetylcholine and induce the catalysis of inositol 1,4,5-triphosphate (IP3) by phospholipase C (PLC) or the catalysis of cyclic adenosine monophosphate (cAMP) by adenylate cyclase (Siegel et al. 1999). These second messengers regulate Ca2+ homeostasis via modulation of plasma membrane and endoplasmic reticulum membrane ion channels (Figure 2). Traditionally, AChE inhibition and disruption of Ca2+ homeostasis have been associated with memory deficit, seizures, and neurodegeneration of hippocampal pyramidal neurons (Ijomone et al. 2019). These observations are consistent with earlier reported associations, showing that anticholinesterase agents not only induce neurodegeneration of pyramidal neurons residing in CA1 hippocampal area, but also potentiated neuronal oxidative damage (Gupta et al. 2007).
Related Knowledge Centers
- Action Potential
- Alpha Motor Neuron
- Axon Terminal
- Glutamic Acid
- Motor Neuron
- Neuromuscular Junction
- Neurotransmitter
- Skeletal Muscle
- Exocytosis
- Acetylcholine