Paranodal dysmyelination and increase in tetrodotoxin binding sites in the sciatic nerve of the motor end-plate disease (med/med) mouse during postnatal development.
Motor end-plate disease (med), in the mouse, is a hereditary neuromuscular defect, caused by a single gene mutation and characterized by a progressive muscle weakness. +Med/+med mice die 21-23 days after birth and the neurobiological abnormalities already reported are nerve terminal sprouting and swelling and neurotransmission failures. We studied +med/+med mice at preclinical (9-11 days after birth) as well as at clinically recognized stages of the disease. The nonmyelinated gaps of the nodes of Ranvier in the +med/+med sciatic nerve are found to be significantly widened in +med/+med animals compared to control littermates, even in the preclinical stage, although the nodes of Ranvier are not yet ultrastructurally mature. The maximal binding capacity for [3H]ethylene-diamine tetrodotoxin, expressed in femtomoles per milligram of protein, is significantly increased in +med/+med sciatic nerves. Thus, Na+ channels, which are known to be located mainly at the nodes of Ranvier in normal myelinated axons, are increased in number in +med/+med mice even before the disease becomes clinically established. Both the ultrastructural and biochemical developmental abnormalities of the node of Ranvier rapidly approach their maximal expression as the behavioral signs develop. Such nerve abnormalities may be closely related to the physiological impairment of nerve impulse conduction which leads to the pathophysiological expression of motor end-plate disease.
D000375:Aging; D000818:Animals; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009045:Motor Endplate; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009469:Neuromuscular Junction; D011901:Ranvier's Nodes / Q000473:pathology; D012584:Sciatic Nerve / Q000378:metabolism / Q000473:pathology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism*
D007473:Ion Channels; D013779:Tetrodotoxin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase