title: Rectification of muscle and nerve deficits in paralyzed ryanodine receptor type 1 mutant embryos.
abstract: Locomotion and respiration require motor axon connectivity and activation of the neuromuscular junction (NMJ). Through a forward genetic screen for muscle weakness, we recently reported an allele of ryanodine receptor type 1 (Ryr1(AG)). Here we reveal a role for functional RyR1 during acetylcholine receptor (AChR) cluster formation and embryonic synaptic transmission. Ryr1(AG) homozygous embryos are non-motile. Motor axons extend past AChR clusters and enlarged AChR clusters are found under fasciculated nerves. Using physiological and pharmacological methods, we show that contractility can be resumed through the masking of a potassium leak, and evoked vesicular release can be resumed via bypassing the defect in RyR1 induced calcium release. Moreover, we show the involvement of ryanodine receptors in presynaptic release at the NMJ. This data provides evidence of a role for RyR1 on both the pre- and postsynaptic sides of the NMJ.
authors.affiliation: Department of Pediatrics University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, United States. Electronic address: martin.hanson@ucdenver.edu.
authors.forename: M
authors.initials: M
authors.lastname: Gartz Hanson
authors.affiliation: Department of Pediatrics University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, United States.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Niswander
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018908:Muscle Weakness / Q000473:pathology; D018482:Muscle, Skeletal / Q000196:embryology / Q000502:physiology*; D009417:Nerve Tissue / Q000378:metabolism; D009469:Neuromuscular Junction / Q000196:embryology* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000502:physiology*; D012119:Respiration; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; C000592747:ryanodine receptor 1, mouse; D011188:Potassium; D002118:Calcium
keywords: Acetylcholine; Diaphragm; Excitation–contraction coupling; Motoneuron