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Synaptic vesicle abnormality in familial infantile myasthenia
Abstract:
In familial infantile myasthenia (FIM) the miniature end-plate potential (MEPP) amplitude is normal in rested muscle, but stimulation in vitro at 10 Hz decreases it abnormally, and neuromuscular transmission fails in a few minutes. In search of a morphologic correlate of the transmission failure, we analyzed the densities and diameters of synaptic vesicles in deep and superficial regions of nerve terminals in external intercostal muscles of three FIM patients and three nonweak controls before and after 10-Hz stimulation for 10 minutes. The densities of superficial or deep synaptic vesicles before or after stimulation in FIM were not significantly different from the corresponding control values. The diameters of superficial and deep synaptic vesicles before stimulation were significantly smaller in the three FIM patients than in the three controls. Stimulation in the FIM patients reduced the MEPP amplitude by 51 to 75%, but increased the vesicle diameter in two patients and did not change the vesicle diameter in one patient. Stimulation in the controls reduced the MEPP amplitude by only 16 to 34%, decreased the vesicle diameter in two, and did not change the vesicle diameter in one. Stimulation after treatment with 1 mg/dl hemicholinium markedly reduced the MEPP amplitude in the controls, had no further effect on the transmission defect in FIM, and had no consistent effect on vesicle diameter in FIM or controls. We conclude that synaptic vesicles are abnormally small in rested muscle in FIM, but vesicle size cannot be reliably correlated with the MEPP amplitude in FIM or controls.
Insights
Familial infantile myasthenia (FIM) is linked to abnormally small synaptic vesicles in nerve terminals. While vesicle size is reduced in FIM patients, it doesn't directly correlate with the severity of neuromuscular transmission defects.
Area of Science:
- Neurology
- Cell Biology
- Neuroscience
Background:
- Familial infantile myasthenia (FIM) presents with neuromuscular transmission failure.
- Abnormalities in synaptic vesicle morphology are suspected in FIM.
- Miniature end-plate potential (MEPP) amplitude is a key indicator of neuromuscular junction function.
Purpose of the Study:
- To investigate the morphological characteristics of synaptic vesicles in FIM.
- To correlate synaptic vesicle size and density with neuromuscular transmission failure in FIM patients.
- To explore the impact of nerve stimulation on vesicle morphology and MEPP amplitude.
Main Methods:
- Analysis of synaptic vesicle density and diameter in nerve terminals of external intercostal muscles.
- Comparison between three FIM patients and three non-weak controls.
- Assessment before and after in vitro nerve stimulation at 10 Hz for 10 minutes.
- Evaluation of MEPP amplitude changes and their correlation with vesicle morphology.
Main Results:
- Synaptic vesicle diameters were significantly smaller in FIM patients compared to controls, even in rested muscle.
- Nerve stimulation reduced MEPP amplitude more severely in FIM patients (51-75%) than in controls (16-34%).
- Vesicle size changes post-stimulation varied and did not consistently correlate with MEPP amplitude reduction in either group.
Conclusions:
- Abnormally small synaptic vesicles are a characteristic morphological feature in rested muscle of FIM patients.
- Synaptic vesicle size alone does not reliably explain the observed MEPP amplitude deficits or transmission failure in FIM.
- Further research is needed to elucidate the precise mechanisms underlying FIM pathophysiology.