Axotomy-like electrophysiological alterations in spinal motoneurons in beta,beta'-iminodipropionitrile neuropathy.
Motoneurons (MNs) exhibit characteristic electrophysiological alterations following axotomy which are concomitants of perikaryal remodeling induced by the axonal injury. beta,beta'-Iminodipropionitrile (IDPN) neurotoxicity, which produces proximal axonal swellings in the first internodes of motor fibers, was studied as a model of perikaryal electrophysiological properties in axonal pathologies without axonal degeneration. Similarities between parameters of MN excitability (delayed depolarizations, repetitive discharge, and the afterhyperpolarization potential, AHP) known to occur in axotomized MN and those in IDPN neuropathy were examined in type-identified spinal MN of cats during the evolution (7 to 35 days) of proximal axonal swellings. Delayed depolarization potentials were observed frequently in fast MN types throughout the neuropathy but only at 35 days in slow MN types. Similarly, repetitive firing occurred most prominently in fast MNs early in the neuropathy. Concomitantly, AHP duration decreased as early as 7 days in all MN types and was significantly shortened in types FF, FR, and S motoneurons. AHP peak amplitude and current declined continuously from 7 to 35 days of the neuropathy and were significantly (p less than 0.05) decreased at 35 days in types FF and S MNs. These results suggest that not only are fast MN types vulnerable early in IDPN neuropathy, but also that all MN types exhibit electrophysiological changes strikingly similar to those following mechanical axotomy. The possibility is raised that IDPN may initiate electrophysiological changes, analogous to perikaryal remodeling, by mechanism(s) unrelated to axonal degeneration.
Delio
D A
DA
Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
Gold
B G
BG
Lowndes
H E
HE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects; D002415:Cats; D009046:Motor Neurons / Q000187:drug effects*; D009570:Nitriles / Q000633:toxicity*
D009570:Nitriles; C008110:3,3'-iminodipropionitrile