Single fiber electromyographic jitter and detection of acute changes in neuromuscular function in young and adult rats.
BACKGROUND
Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapted single fiber electromyography (SFEMG) techniques to quantify neuromuscular jitter in adult and juvenile rats after treatment with agents that alter cholinergic neurotransmission.


METHODS
Anesthetized adult and juvenile rats were tested using stimulation SFEMG, recorded in the gastrocnemius muscle, after stimulation in the sciatic notch region. The influence of electrode placement, treatment with decamethonium (to disrupt neuromuscular transmission) or physostigmine (reversible ChE inhibitor), and the impact of varied stimulation frequency were quantified.


RESULTS
No significant effects of needle placement or criterion amplitude were observed when calculating the mean consecutive difference (MCD). Treatment with decamethonium did not alter MCD values in adult or juvenile rats. However, decamethonium produced an increased blocking of muscle action potentials (MAP) in juveniles. Also, when stimulated at 9.09 Hz, both adult and juvenile animals had a greater decrease in MAP amplitude between the first and fourth responses (T(1)-T(4) decrement) after treatment with decamethonium. Prior to treatment with decamethonium, the T(1)-T(4) decrement averaged about 3 fold greater in juveniles than adults, and was larger at 3.03 and 9.09 Hz than with 0.91 Hz stimulation. Treatment with physostigmine resulted in at least 50% inhibition of muscle ChE activity, but produced minimal changes in the MCD values in adults or juveniles. Combined over treatments and stimulation frequencies, the median MCD for juveniles (11.6 micros) was less than that for of adults (18.8 micros). In juveniles, the median MCD increased from 9.3 micros to 13.9 micros as the stimulation rate was increased from 0.91 to 9.09 Hz. This stimulus-dependent change was more evident in juveniles than in adults.


CONCLUSIONS
A technique was developed to record stimulation SFEMG and neuromuscular jitter, in vivo, in adult and juvenile rats. The method was sufficiently sensitive to detect age-related differences, potentially allowing developmental processes to be examined. Based on the literature and the current data, the technique appears to be more sensitive to prolonged inhibition of ChE enzymes than the reversible inhibition produced by physostigmine.
Toxicology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. dbfinley@bellsouth.net
Dana B
DB
Finley
Xiaochun
X
Wang
Jaimie E
JE
Graff
David W
DW
Herr
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003650:Decamethonium Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004576:Electromyography / Q000295:instrumentation / Q000379:methods*; D005260:Female; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D010830:Physostigmine / Q000494:pharmacology; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D002800:Cholinesterase Inhibitors; D003650:Decamethonium Compounds; D009466:Neuromuscular Blocking Agents; D009467:Neuromuscular Depolarizing Agents; D010830:Physostigmine; C033019:decamethonium