Motor unit function during evolution of proximal axonal swellings.
beta,beta'-Iminodipropionitrile (IDPN) impairs axonal transport of neurofilaments; their accumulation leads to the formation of proximal swellings in motor axons. Similar proximal swellings are a feature of some cases of motor neuron disease such as amyotrophic lateral sclerosis (ALS). Motor units in IDPN-treated animals were assessed to determine their relative susceptibilities to impaired function and whether the functional changes resulting from proximal axonal swellings share certain electromyographic features with ALS. Intrinsic properties of medial gastrocnemius motoneurones (MN) and contractile responses of their motor units were examined during the evolution of proximal axonal swellings in cats administered IDPN (50 mg/kg once weekly) for 7, 14 or 35 days. While conduction velocities were significantly decreased in all motor unit types by 35 days, the conduction slowing was greater in fast fatigable (types FF and FI) motor units than in fatigue resistant (types FR and S) motor units. Normal correlations between axonal conduction velocity and MN input resistance (Rin) and the inverse relationship between Rin and rheobase were lost with progression of the neuropathy. Twitch and maximum tetanic tension developed by fast-fatigable motor units declined early in the neuropathy, whereas fatigue-resistant units did not show similar changes until later stages of the intoxication. In some motor units, irregular and abnormal tetanic tensions were elicited by repetitive MN discharge. At 14 and 35 days, a novel, intermediate motor unit response classified as slow and fatigable (SF) was observed. Conduction block, characterized by repetitive MN firing without a corresponding contractile response, was observed in some type FF and S units by 35 days. Morphometric analysis of muscle fiber types showed significant atrophy, particularly in the type I fibers at 14-35 days; the atrophy reversed following cessation of IDPN administration. The influence of proximal axonal swellings on motor unit function in IDPN neuropathy is discussed in terms of reported electrophysiological alterations in motoneurone disease.
Delio
D A
DA
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, NJ 08855-0789.
Fiori
M G
MG
Lowndes
H E
HE
D000200:Action Potentials; D000690:Amyotrophic Lateral Sclerosis; D000818:Animals; D001284:Atrophy; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000473:pathology*; D002415:Cats; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005260:Female; D008297:Male; D016472:Motor Neuron Disease; D009046:Motor Neurons / Q000502:physiology* / Q000648:ultrastructure; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology / Q000633:toxicity*; D009570:Nitriles / Q000494:pharmacology / Q000633:toxicity*
D016900:Neurofilament Proteins; D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile