Ectopic impulse generation in dorsal root ganglion neurons during methylmercury intoxication: an electrophysiological and morphological study.
Electrophysiological function and morphology of dorsal root ganglion (DRG) neurons were investigated in female Wistar rats following administration of methylmercury (5 mg/kg/day for 10 days). Neurons were classified according to the conduction velocities of their peripheral axons and perikaryal action potential characteristics as types A alpha, A beta A delta and C. In methylmercury-treated rats, the majority of DRG neuron action potential characteristics were not significantly altered. However, axonal conduction velocities were slowed in all type A ganglion cells, leading to significant delays in action potential onset in types A beta and A delta neurons. An initial complex-soma inflection was observed on the rising phase of the action potential of some cells. These inflection potentials had longer conduction times and lower amplitudes in treated animals. Repetitive discharge, characterized by 3-5 action potentials upon single peripheral nerve stimulation, was observed in 8 of 38 cells recorded in treated animals, predominantly in type A beta (4/8) and A beta (3/12) neurons; direct current injection into repetitively discharging cells via the recording electrode elicited only single action potentials. Extracellular recordings from dorsal root filaments confirmed that the repetitive action potentials arising in the DRG were conducted to the spinal cord. Morphological examination of DRG revealed damage in up to 10% of neurons, consisting of loss of Nissl staining, cytoplasmic vacuolization, and proliferation of satellite cells. Large, pale neurons appeared preferentially involved. Rarely, neuronophagia was observed. Further microscopic examination of proximal and distal sections of sciatic and tibial nerves revealed only occasional degeneration of myelinated axons. While morphological alterations did not appear to offer a structural basis for the multiple firing, it is speculated that repetitive action potential discharge may contribute to the paresthesias associated with MeHg intoxication.
Delio
D A
DA
Department of Pharmacology and Toxicology, Rutgers University College of Pharmacy, Piscataway, New Jersey 08854.
Reuhl
K R
KR
Lowndes
H E
HE
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008767:Methylmercury Compounds / Q000506:poisoning*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D008767:Methylmercury Compounds