title: Reduced neuromuscular quantal content with normal synaptic release time course and depression in canine motor neuron disease.
abstract: Hereditary canine spinal muscular atrophy is an autosomal dominant version of motor neuron disease in which motor units exhibit extensive dysfunction before motor terminal or axonal degeneration appear. We showed in a previous paper that motor endplate currents (EPCs) are reduced and that failures of nerve-evoked EPCs appear in the homozygote medial gastrocnemius (MG) muscle in which failing motor units are also found, suggesting a presynaptic deficit of ACh release. To examine this further, we performed a detailed analysis of synaptic release properties in the MG muscle of homozygotes and compared the results with data from genetically normal control animals. We found that the amplitude of miniature EPCs (mEPC) did not differ between homozygote and normal synapses, indicating that quantal content is reduced at homozygote motor terminals. Consistent with this, deconvolution analysis showed that the maximum release rates at homozygote motor terminals were significantly reduced relative to normal. This analysis also demonstrated that the time course of quantal release at homozygote synapses did not differ from normal. The extent of quantal release depression during high-frequency activation in homozygotes did not differ from normal despite the significant reduction of quantal content and maximum release rate. Surprisingly, the absolute amount of posttetanic potentiation was not decreased at homozygotes motor terminals despite the differences in quantal content. We conclude that failure of homozygote motor unit force during repetitive activity is due to a unique combination of low quantal content and normal release depression and suggest that the primary deficit in homozygote motor terminals is a reduced supply of readily releasable quanta.
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Rich
authors.forename: Xueyong
authors.initials: X
authors.lastname: Wang
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Cope
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pinter
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics* / Q000503:physiopathology*; D004285:Dogs; D004553:Electric Conductivity; D004558:Electric Stimulation; D006720:Homozygote; D008959:Models, Neurological; D009045:Motor Endplate / Q000503:physiopathology; D016472:Motor Neuron Disease / Q000662:veterinary*; D009469:Neuromuscular Junction / Q000503:physiopathology*; D012016:Reference Values; D013569:Synapses / Q000502:physiology*; D013997:Time Factors