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Muscle cells become stronger by expanding myofibrils, the chains of sarcomeres that produce contraction. Here we investigate how Mylpf (Myosin Light Chain Phosphorylatable Fast) abundance impacts myofibril assembly in fast-twitch muscle. The two zebrafish Mylpf genes ( mylpfa and mylpfb ) are exclusively expressed in fast-twitch muscle. We show that these cells initially produce six times more mylpfa mRNA and protein than mylpfb . The combined Mylpf protein dosage is necessary for and proportionate to fast-twitch myofibril growth in the embryo. Fast-twitch myofibrils are severely reduced in the mylpfa -/- mutant, leading to loss of high-speed movement; however, by persistent slow movement this mutant swims as far through time as its wild-type sibling. Although the mylpfb -/- mutant has normal myofibrils, myofibril formation fails entirely in the mylpfa -/- ; mylpfb to a degree corresponding linearly with GFP brightness. This correlate is inverted by expression of -/- double mutant, indicating that the two genes are collectively essential to myofibril formation. Fast-twitch myofibril width is restored in the mylpfa -/- mutant by transgenic expression of mylpfa-GFP, mylpfb-GFP , and by human MYLPF-GFP to a degree corresponding linearly with GFP brightness. This correlate is inverted by expression of MYLPF alleles that cause Distal Arthrogryposis, which reduce myofibril size in proportion to protein abundance. These effects indicate that Mylpf dosage controls myofibril growth, impacting embryonic development and lifelong health., Competing Interests: Competing Interest Statement The authors declare that they have no competing interests.

Background: Myopathies are generally considered to increase the risk for succinylcholine-induced hyperkalaemia and may affect the duration of action of neuromuscular blockers. Centronuclear (myotubular) myopathy (CNM) is congenital and produces various degrees of muscular weakness and associated complications such as respiratory failure. The effects of succinylcholine and the potentially lethal consequences of hyperkalaemia on patients with CNM are unknown due to its rarity. One source of information is the dog, as CNM occurs naturally in dogs. Because of its remarkable similarity with the disease in man, canine CNM can serve as a model to further our knowledge of the effects of succinylcholine., Objectives: We examined the kalaemic and neuromuscular effects of succinylcholine in dogs with and without autosomal-recessive CNM., Design: A prospective, experimental study., Setting: Anaesthesiology laboratory, College of Veterinary Medicine, Cornell University, New York, USA., Patients: Six dogs with autosomal-recessive CNM and six control dogs., Interventions: Dogs received succinylcholine 0.3 mg kg during isoflurane anaesthesia., Main Outcome Measures: Whole blood potassium concentration was measured 5 min before and after succinylcholine administration. Neuromuscular function was measured with acceleromyography and single twitch stimulation., Results: All dogs recovered uneventfully from anaesthesia. The increase in potassium concentration [mean (SD)] following succinylcholine was similar between groups: CNM 0.5 (0.4) mmol l and control 0.7 (0.4) mmol l (P = 0.47). Recovery of the single twitch to 25, 75 and 90% was longer in the CNM group (all P < 0.001); 90% recovery took 35.5 (1.18) min for the CNM group and 23.3 (1.68) min for the control group., Conclusion: CNM did not exacerbate the increase in blood potassium that is ordinarily seen with succinylcholine. Recovery from succinylcholine was nearly 50% longer in dogs with CNM. Although our sample size is too small to evaluate the incidence of succinylcholine-induced hyperkalaemia, extrapolation of these findings suggests that increased duration of action should be expected if succinylcholine is given to a patient with autosomal-recessive CNM.

Objective: Quantitative neuromuscular monitoring is essential for studies of potency and duration of neuromuscular blocking agents, and for detecting residual paralysis in anesthetized patients. This investigation evaluates whether there are systematic differences between acceleromyography (AMG) and electromyography (EMG); two quantitative methods for monitoring neuromuscular block., Study Design: Prospective., Animals: Ten healthy Beagle dogs., Methods: Dogs were anesthetized with isoflurane and dexmedetomidine. Both ulnar nerves were stimulated with a train-of-four (TOF) pattern every 15 seconds. The magnitude of the first twitch (T1) and the TOF ratio (magnitude of T4/T1; TOFR) were quantified simultaneously with AMG and EMG, applied randomly to each extremity. The extent of maximal block (T1 depression) and onset time were measured by AMG and EMG during TOF monitoring after the administration of cisatracurium (0.05 mg kg(-1)). In addition, recovery of T1 to 25% and 75%, the recovery index (time between T1 of 25% and 75%), and recovery of the TOFR to 0.9 were used to characterize recovery from cisatracurium and were compared between monitors. Regression and Bland-Altman plots for T1 and TOFR were also created., Results: Maximal block and onset time were not different between monitors. Time to recovery of T1 to 25% and 75%, and time to TOF ratio 0.9 was significantly shorter with AMG. The recovery index was not different between monitors. When the TOFR returned to 0.9 with AMG, EMG still measured considerable residual block (TOFR 0.47)., Conclusions and Clinical Relevance: Electromyography consistently detected residual NMB when recovery from NMB was complete as assessed by AMG., (© 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.)

Objective: To evaluate the potency of vecuronium and duration of vecuronium-induced neuromuscular blockade in dogs with centronuclear myopathy (CNM)., Animals: 6 Labrador Retrievers with autosomal-recessive CNM and 5 age- and weight-matched control dogs., Procedures: Dogs were anesthetized on 2 occasions (1-week interval) with propofol, dexmedetomidine, and isoflurane. Neuromuscular function was monitored with acceleromyography and train-of-four (TOF) stimulation. In an initial experiment, potency of vecuronium was evaluated by a cumulative-dose method, where 2 submaximal doses of vecuronium (10 μg/kg each) were administered IV sequentially. For the TOF's first twitch (T1), baseline twitch amplitude and maximal posttreatment depression of twitch amplitude were measured. In the second experiment, dogs received vecuronium (50 μg/kg, IV) and the time of spontaneous recovery to a TOF ratio (ie, amplitude of TOF's fourth twitch divided by amplitude of T1) ≥ 0.9 and recovery index (interval between return of T1 amplitude to 25% and 75% of baseline) were measured., Results: Depression of T1 after each submaximal dose of vecuronium was not different between groups. Median time to a TOF ratio ≥ 0.9 was 76.7 minutes (interquartile range [IQR; 25th to 75th percentile], 66.7 to 99.4 minutes) for dogs with CNM and 75.0 minutes (IQR, 47.8 to 96.5 minutes) for controls. Median recovery index was 18.0 minutes (IQR, 9.7 to 23.5 minutes) for dogs with CNM and 20.2 minutes (IQR, 8 to 25.1 minutes) for controls., Conclusions and Clinical Relevance: For the study dogs, neither potency nor duration of vecuronium-induced neuromuscular blockade was altered by CNM. Vecuronium can be used to induce neuromuscular blockade in dogs with autosomal-recessive CNM.