Passage
The nicotinic acetylcholine receptor (nAChR) is a protein embedded in the muscle fiber membrane that facilitates cell-to-cell communication across the neuromuscular junction. When acetylcholine (ACh) binds nAChR, electrical depolarization within skeletal muscle fibers is induced and ultimately gives rise to contractile activity. The nAChR is composed of five protein subunits symmetrically organized around a central ion pore. Previous studies demonstrated that these subunits may serve as epitopes (antibody binding sites) in autoimmune disease. By reversibly binding nAChR subunits, anti-nAChr antibodies may temporarily block the attachment site for ACh, resulting in muscle weakness.Researchers harvested muscle samples from mice to investigate the effects of anti-nAChR antibodies on muscle tension, the pulling force transmitted by muscles during contraction.Experiment 1First, skeletal muscle samples (tibialis anterior) of adult male mice were surgically harvested (n = 30) , washed, and stripped of connective tissues. Next, the isolated muscle samples were placed in a 150-mL oxygen-infused, electrolyte-rich bath containing glucose and Ca²⁺ ions that were able to enter the muscle fibers and enable maximal contractile force. One end of the submerged muscle was anchored in place while the other was attached to an apparatus that measures muscle tension and modifies muscle length. Using electrodes, action potentials were elicited in the harvested muscle tissue to evaluate contractile function (Figure 1) .
Figure 1 Action potential elicited from a harvested skeletal muscle sampleExperiment 2The researchers divided the 30 muscle samples into three groups of 10. Resting muscle tension was measured, and the electrolyte-rich baths of each group were further infused with a 7.5-mL solution containing mouse-specific anti-nAChR antibodies, ACh, or a mixture of both (Table 1) . Post-infusion (peak) muscle tension was measured for 30 minutes, with results displayed in Figure 2.Table 1 Solutions Infused into the Electrolyte-Rich Bath
Figure 2 Pre-infusion resting muscle tension and post-infusion peak muscle tension in harvested muscle samples (Note: * indicates p < 0.05.)
-A mutant mouse is found to exhibit normal musculoskeletal function following the administration of anti-nAChR antibodies. Compared to a wild-type mouse, this mutant mouse is most likely to show which of the following changes at the neuromuscular junction?

Question

Passage
The nicotinic acetylcholine receptor (nAChR) is a protein embedded in the muscle fiber membrane that facilitates cell-to-cell communication across the neuromuscular junction. When acetylcholine (ACh) binds nAChR, electrical depolarization within skeletal muscle fibers is induced and ultimately gives rise to contractile activity. The nAChR is composed of five protein subunits symmetrically organized around a central ion pore. Previous studies demonstrated that these subunits may serve as epitopes (antibody binding sites) in autoimmune disease. By reversibly binding nAChR subunits, anti-nAChr antibodies may temporarily block the attachment site for ACh, resulting in muscle weakness.Researchers harvested muscle samples from mice to investigate the effects of anti-nAChR antibodies on muscle tension, the pulling force transmitted by muscles during contraction.Experiment 1First, skeletal muscle samples (tibialis anterior) of adult male mice were surgically harvested (n = 30) , washed, and stripped of connective tissues. Next, the isolated muscle samples were placed in a 150-mL oxygen-infused, electrolyte-rich bath containing glucose and Ca²⁺ ions that were able to enter the muscle fibers and enable maximal contractile force. One end of the submerged muscle was anchored in place while the other was attached to an apparatus that measures muscle tension and modifies muscle length. Using electrodes, action potentials were elicited in the harvested muscle tissue to evaluate contractile function (Figure 1) .

Figure 1 Action potential elicited from a harvested skeletal muscle sampleExperiment 2The researchers divided the 30 muscle samples into three groups of 10. Resting muscle tension was measured, and the electrolyte-rich baths of each group were further infused with a 7.5-mL solution containing mouse-specific anti-nAChR antibodies, ACh, or a mixture of both (Table 1) . Post-infusion (peak) muscle tension was measured for 30 minutes, with results displayed in Figure 2.Table 1 Solutions Infused into the Electrolyte-Rich Bath

Figure 2 Pre-infusion resting muscle tension and post-infusion peak muscle tension in harvested muscle samples (Note: * indicates p < 0.05.)
-A mutant mouse is found to exhibit normal musculoskeletal function following the administration of anti-nAChR antibodies. Compared to a wild-type mouse, this mutant mouse is most likely to show which of the following changes at the neuromuscular junction?

Quizplus · Accepted Answer

11ecba2d_100d_b09f_a3bf_9fc62457bf77_MD0008_00 The interface between a somatic motor neuron and a skeletal muscle fiber is a specialized synapse known as the neuromuscular junction (NMJ). The basic function of the NMJ is to convert a motor neuron action potential into a muscle fiber action potential. Activity at the NMJ begins on the presynaptic side. The arrival of an action potential at the axon terminal of the presynaptic motor neuron triggers a series of processes that result in the release of ACh from presynaptic vesicles and into the synaptic cleft via exocytosis. ACh diffuses across the synaptic cleft to bind nicotinic ACh receptors (nAChRs) embedded within the membrane of the postsynaptic muscle fiber, eventually leading to muscle contraction. Unbound ACh may diffuse away from the synapse or be degraded by the enzyme acetylcholinesterase (AChE), terminating muscle fiber contraction. Based on the passage, anti-nAChR antibodies bind nAChR reversibly to block the interaction between ACh and nAChR, resulting in muscle weakness. Accordingly, administration of these antibodies in a wild-type mouse would temporarily prevent binding of ACh to its receptor. However, if a mutant mouse were to exhibit normal muscle contraction despite being treated with anti-nAChR antibodies, the most likely reason in this scenario is that ACh degradation within the mutant's synapse would be decreased compared to the wild-type. If ACh degradation is decreased, more ACh molecules will remain in the synapse for a longer time period and be able to bind nAChRs after these are no longer bound to anti-nAChR antibodies. This would result in muscle contraction that is delayed but still normal. In contrast, the following changes would magnify the inhibitory effect of anti-AChR antibodies on muscle contraction by decreasing the likelihood of ACh binding to nAChR: Fewer nAChR being present within the postsynaptic membrane decreases the binding sites available to synaptic ACh, resulting in muscle weakness (Choice B). Following motor neuron action potentials, reduced release of ACh from the presynaptic vesicles and decreased recycling of ACh breakdown products would decrease the quantity of ACh released into the synapse, also leading to muscle weakness (Choices C and D). Educational objective: Acetylcholine (ACh) degradation within the neuromuscular junction is one process by which muscle fiber contraction is terminated. However, decreased ACh degradation would allow more ACh molecules to remain in the synapse and prolong stimulation of nAChR and subsequent muscle contraction.

Passage the Nicotinic Acetylcholine Receptor (NAChR) Is a Protein Embedded in in the Muscle