Rectification of muscle and nerve deficits in paralyzed ryanodine receptor type 1 mutant embryos

Autor: Lee Niswander, M. Gartz Hanson
Rok vydání: 2015
Předmět:
Synaptic Transmission
Mice
0302 clinical medicine
Postsynaptic potential
Receptors
Cholinergic
Nerve Tissue
Axon
Mice
Knockout
Motor Neurons
0303 health sciences
Muscle Weakness
Ryanodine receptor
Respiration
musculoskeletal system
Motoneuron
Cell biology
medicine.anatomical_structure
tissues
Locomotion
Acetylcholine
Muscle Contraction
medicine.drug
medicine.medical_specialty
animal structures
Diaphragm
Neuromuscular Junction
Neurotransmission
Biology
Article
Neuromuscular junction
Excitation–contraction coupling
03 medical and health sciences
Internal medicine
medicine
Animals
Muscle
Skeletal
Molecular Biology
030304 developmental biology
Acetylcholine receptor
RYR1
fungi
Ryanodine Receptor Calcium Release Channel
Cell Biology
Mice
Inbred C57BL
Endocrinology
Potassium
Calcium
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Developmental Biology. 404:76-87
ISSN: 0012-1606
DOI: 10.1016/j.ydbio.2015.05.018
Popis: 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 (Ryr1AG). Here we reveal a role for functional RyR1 during acetylcholine receptor (AChR) cluster formation and embryonic synaptic transmission. Ryr1AG 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.
Databáze: OpenAIRE
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