Morphology of neuromuscular junction in patients with peripheral artery disease

Peripheral artery disease (PAD) is primarily caused by occlusion of arteries that supply blood to the lower limbs and presents significantly pathological changes of calf muscles, include degenerating and regenerating fibers, reduction of the skeletal muscle area, connective tissue proliferation and fibrosis, fat accumulation, and abnormal mitochondria, all of which are predictors of muscle functional decline. Additionally, skeletal muscles also require the motor nerve innervation for the signal transmission through the neuromuscular junction (NMJ) to induce skeletal muscle contraction. To observe whether the NMJ is changed in the PAD patients, gastrocnemius muscles were collected from 2 health subjects and 6 PAD stage III/IV patients. The motor nerve terminals were labeled with anti-neurofilament 200 and anti-synaptophysin antibodies, the nicotinic acetylcholine receptors (nAChRs) were labeled with α-Bungarotoxin. Labeled NMJs were imaged using a laser scanning confocal microscope with Z-stack. The image was captured in 65 NMJs from health subjects and 140 NMJs from PAD patients, respectively. The total nAChR area and the number of discrete fragments of each nAChR cluster, the area per fragment, the percentage of fragmented nAChR clusters, the nerve innervation and the nerve terminal occupancy were calculated. The results were represented with mean ± standard error (SE). The nAChR area was 354.9 ± 12.7 and 209.4 ± 8.2, the average number of fragment/ nAChR cluster was 2.6 ± 0.2 and 3.1 ± 0.2, 6.2% and 19.3% of the nAChR clusters were fragmented, and the nerve terminal occupancy was 61.5 ± 1.4 % and 52.0 61.5 ± 1.8 in the health subjects and PAD patients, respectively. All nAChR clusters were innervated by the motor nerve terminal in the health subjects, whereas 8.6% of nAChR clusters were denervated in PAD Patients. These data indicate that the total nAChR area per nAChR cluster and the area of each discrete fragment are reduced and fragmented nAChR clusters are increased in PAD patients. Additionally, the denervation of nAChR clusters is increased in PAD patients. These results suggest that the neuromuscular transmission is compromised in PAD patients, which limits patients’ physical activities. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.