TY - JOUR
T1 - Role of recovery of acetylcholine release in compromised neuromuscular junction function
AU - Winther, Jeppe Blichfeldt
AU - Morgen, Jeanette Jeppesen
AU - Skov, Martin
AU - Broch-Lips, Martin Gruwier
AU - Nielsen, Ole Bækgaard
AU - Overgaard, Kristian
AU - Pedersen, Thomas Holm
N1 - Publisher Copyright:
© 2024
PY - 2024/3
Y1 - 2024/3
N2 - Everyday physical activities, such as walking, are enabled by repeated skeletal muscle contractions and require a well-functioning neuromuscular transmission. In myasthenic disorders, activities of daily living are debilitated by a compromised neuromuscular transmission leading to muscle weakness and fatiguability in patients. To enable physical activity, acetylcholine (ACh) is released repeatedly from the motor nerve, however, the role of the nerve terminals’ capacity to sustain ACh release to support repetitive contractions under compromised neuromuscular transmission remains unclear. To explore this, we studied synaptic and contractile function during repeated contractions in healthy rat skeletal muscles under conditions of pharmacological induced compromised neuromuscular transmission. Using recordings of endplate potentials, compound muscle action potential (CMAP) and force production in isolated skeletal muscles and living, anesthetized animals, we found that force and CMAP were markedly reduced by even very light activity performed up to 5 s prior to contraction showing that recovery of ACh release was insufficient to maintain synaptic transmission strength. Our results suggest that the timing of depletion and restoration of ACh release may impact clinical signs of weakness and fatigability in patients with impaired neuromuscular transmission and affect the sensitivity of electromyographic recordings in the clinic.
AB - Everyday physical activities, such as walking, are enabled by repeated skeletal muscle contractions and require a well-functioning neuromuscular transmission. In myasthenic disorders, activities of daily living are debilitated by a compromised neuromuscular transmission leading to muscle weakness and fatiguability in patients. To enable physical activity, acetylcholine (ACh) is released repeatedly from the motor nerve, however, the role of the nerve terminals’ capacity to sustain ACh release to support repetitive contractions under compromised neuromuscular transmission remains unclear. To explore this, we studied synaptic and contractile function during repeated contractions in healthy rat skeletal muscles under conditions of pharmacological induced compromised neuromuscular transmission. Using recordings of endplate potentials, compound muscle action potential (CMAP) and force production in isolated skeletal muscles and living, anesthetized animals, we found that force and CMAP were markedly reduced by even very light activity performed up to 5 s prior to contraction showing that recovery of ACh release was insufficient to maintain synaptic transmission strength. Our results suggest that the timing of depletion and restoration of ACh release may impact clinical signs of weakness and fatigability in patients with impaired neuromuscular transmission and affect the sensitivity of electromyographic recordings in the clinic.
KW - Compromised neuromuscular transmission
KW - Fatigability
KW - Muscle weakness
KW - Recovery of acetylcholine release
KW - Repetitive nerve stimulation
UR - http://www.scopus.com/inward/record.url?scp=85185551109&partnerID=8YFLogxK
U2 - 10.1016/j.nmd.2024.01.007
DO - 10.1016/j.nmd.2024.01.007
M3 - Journal article
C2 - 38359767
AN - SCOPUS:85185551109
SN - 0960-8966
VL - 36
SP - 48
EP - 59
JO - Neuromuscular Disorders
JF - Neuromuscular Disorders
ER -